You Say, a Poem by Gigi Sala

He used to sit a few desks behind me in high school. I believe we liked each other but we never became close. I forgot about him for the last 40 plus years. Than a classmate send me his poems, in Italian, asking if I remember him. I immediately remembered Gigi’s smile, it was like I just left him the day before and was about to see him again tomorrow at school. I still do not know much about him and what happened to him during the interval but I hope to see him soon when back in my Old Milan. I would like to know what turned him into a poet? For now I am just posting one of his poems (of course with his permission) and my poor translation of it in English (I truly cannot write poetry). Perhaps, somebody could do a better job and I will be happy to exchange this for a better version.

 

Gigi mia foto fumtizzatajpg

Gigi’s Self Portrait

 

TU DICI

Dici che mi vuoi bene, che tieni a me

Forse come un padrone tiene

Al suo cane zoppo, ringhioso

 

Forse come si tiene

alle cianfrusaglie comprate

Anni prima

Fastidiose e commoventi

Testimoni di un momento

Che non si riesce a buttare

 

Abbozzi un sorriso

Mi guardi con stanchezza

Tu così sensibile, accogliente

E magistralmente indifferente

 

Offensiva nel tuo ottimismo

Prepotente e pietosa

Con il peso di una vita sempre

Occupata

 

Mi spiace, per te,

non saprai mai che sentono i cani

quando guardano da sotto in su

 

che pensano le cianfrusaglie

spolverate ogni tanto

 

che rimuginano le statuine

di terracotta

 

lasciate sole ad affrontare

il tempo.

 

 

YOU SAY

You say that you love me, that you care for me

Perhaps like the master cares

For his limping growling dog,

 

Perhaps like one cares

For the grimcrackery bought

Years passed

Vexing and dear

Witness of moments

That one can’t trash

 

You draft a smile

You look at me with fatigue

You, so sensitive, inviting

And majestically indifferent

 

Offensive in your optimism

Tyrant and merciful

With the weight of a life always

Busy

 

I am sorry for you

You will never now how dogs feel

When the look up from the bottom

 

What do objects feel

When they are seldom dusted

 

What do clay statues

Ruminate

 

Left alone to encounter

The time

 

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The Strange Case of Clara’s Eyes (Part 1)

After a long absence I am back! Here comes the first part of the Strange Case of Clara’s Eyes as a continuation of the series of stories: “A walk in the Park“, The Old Boys Academy” and “Sabrina“. Here Luca’s reveals his secret to …well, you will find out if you bother reading the story to the end.

The unsolitedet flowers HR

The unsolicited flower with chickens – From the author’s backyard – Photo by F. Marincola, Half Moon Bay (El Granada), California, August 6, 2017

The Strange Case of Clara’s Eyes

(Continued from Sabrina)

“In the solitude I observe my own image echoed by thousands of mirrors. I am chased by the squander of anonymity while above hover, staring at me, smiling Clara’s eyes. She was an angel who lasted just for a day; like a dragonfly. Yet, in those moments, so many of hers transpired. I observed multiplicities of smiles, hints of cries, myriads of misgivings and hesitations …and of hopes and joys …and of sorrows …all shining, like stars in the sky, in the depth of her eternal eyes.”

Thus was Luca garbling in barely coherent terms toward to the interlocutor at the “White Truffle Bar” in Corso Venezia, who was in turn impassively staring at him with glacial eyes.

“My life is a splendid tale of lost opportunities,” Luca continued “…like those nightmares when one brawls to escape but the feet don’t follow and stubbornly stick to the ground. When one wants to climb the mountain, where on top shines the statue of hope, but the arms and legs do not obey; when one wants to catch the colors of a butterfly to no avail because all that is …all that it is …it is just a vaporizing mist.

…Like the butterfly, Clara never happened; it was a delusion born out of an occasional encounter that never recurred. When she opened her eyes at the Giardini Pubblici and mine were drawn into hers, I took a glance at a world not to be encountered again. I can’t explain what it was. Perhaps, it was the revelation of love, the reunion of the split hermaphrodites, the fusion of two bodies into a single soul. In her silent eyes I saw my own reflection reverberate for a few perpetual moments.

Her eyes looked straight into mine as if they were searching my soul and it seemed to me that they were inspecting with empathy and gravity at once as if they were trying to retrieve the lost self, that separated from her long time before, in times so far away that they were impervious to any memory and echoed only in the cosmic background of the unconscious. There was a heavenly calm in their warmth. There was the patience of sorrow, a strained optimism in the melancholic smile that accompanied her gaze trying to compensate for the anguish of long sleepless nights spent in solitude and despair. All of that I recognized in that glance and all seemed familiar to me.

That night, I could not sleep but continued to meet her eyes staring at me, and I saw a speechless love that thrives on desire and hope.

… It was a scrawny boy who deterred me from pursuing her. He wanted her more than I did, or so I believed …then. The little thing challenged me! He even punched me with a girlish but determined fist! And I thought: who am I to fight this? Would I ever been able to love a woman that much to reproduce this impulsive act? Would I ever have the courage to confront not this minuscule rival but the ridicule in front of my peers for arguing over a petty skirt? Why would I risk the laughter to win a girl when so many of them are longing for me out there?

That is what I thought! Just as shallow as that!

As a youngster, I was taught self-control, insightfulness, and introspection, something that the grown ups précised as “maturity”. I was jaded over spontaneity and passion: all childlike feelings, unsophisticated emotions suited for the masses. And love!!!! What was love? True love comes with maturity, it will come one day, some unspecified day, when a child turns into a man, when all dreams vanish and conformism takes over and the right companion is chosen to proceed toward the predetermined path where the script of life demands for an uncreative wallpaper to decorate an otherwise perfectly pointless existence.

But then, on those youth days, I could have embraced my choice! I could have deviated from the programmed path! But I didn’t! In the public gardens one is not supposed to pick flowers. It is against the law. So why should one deviate and pick the flower of all flowers on the breeze of the moment? …How would I have known that a lifetime would go by, a consumption of days would flow interminable leaving me wonder over and over about Clara and her eyes: that Clara, who was not …who simply wasn’t just another girl?

In the days that followed, I noticed her repeatedly during the last year of high school, diluted among her friends and yet standing above all of them. But consistently, as soon as those eyes encountered mine, looking straight into my soul I turned my gaze away. Why? I don’t know. It was the scrawny boy, his passion that defeated me. He carried something that I had been deprived of in my sophisticated upbringings. And I waited, I considered, and I reflected while the train was leaving the station, the gazelle ran, the butterfly flew away, and the seagull hovered unreachable in the blue sky. By the time I reckoned what Clara meant, she had long vanished. And from then on, I have been searching for her.”

***

“We sacrifice our existence at the altar of conventionality, we are the heroes of emptiness, the crusaders of the lost battles, getting to the battlefield when the war is over, …and all of this suits us just as well because we never learned, in the sophistication of our upbringing, the value of earning through sweat, by dirtying our hands and breaking our bones with hard labor. So we do not cherish what we receive as granted. It is the entitlement to happiness, which makes it trivial and hollow. Just as well, we do not take risks because we believe that we possess all that we need and we do not want to lose such privilege. We much prefer to avoid the embarrassment of failure by walking the beaten path, where risks are abated and successes are predetermined. We follow this in every aspect of our life, …including love. And I conformed too …and this is why I lost Clara. I confused her for an ordinary poppy among thousands that peak their head barely above the grass along the anonymous street. I did not appreciate that she was the one; the one to pick against the orthodoxy. That I should have had the promptness to recognize the chance to change my path and trespass the forbidden barrier, just like the botanist did to follow the homonymous analphabet Clara in Capek’s story; the Clara who found the exotic blue chrysanthemum in the forgotten valley that he had missed over and over because of the “do not trespass sign”. But Clara could not read and went where his sophistication would not dare to go.

…And now Clara’s eyes and their memory is all that is left; those eyes, her inquisitive eyes keep staring at me as a memento of lost opportunities, of the chance I had to embrace love, the companionship of a life time, the soul mate that legitimizes our existence. Do you know what I mean?”

The interlocutor pithily answered:

“Of course I know what you mean! I know the human soul better than anybody else! I listened to stories like this one millions of times.”

 

The Life (by Jamie Marincola)

Here comes “The Life” a new short story by Jamie Marincola. It reminds me of “The impostor syndrome” but with a totally different twist! I hope you will enjoy it! Thanks Jamie.

 

Funeral with Carabinieri HR

Funeral of a Carabiniere in front of the Cathedral of Pizzo – July, 2017. Photo by F. Marincola

 

The Life

It was a warm winter morning. The kind of morning you don’t mind getting out of bed in the dark. Jerry got out of bed that morning and died. He took off the few bits of clothes he had slept in, jumped in the shower, and died. Something about the warm water on his skin made him faint and hit his head as he went to the ground. The doctors said he had a stroke, but it was definitely the impact of his skull on the side of the shower that did him in. His wife called the EMTs who brought him to the hospital, but it really didn’t matter: he was already quite dead.

Jerry woke up in the afterlife. This was a new experience for Jerry. He was born and raised a Christian, but never believed in any of it. By the time he died, he was thoroughly atheist, or perhaps agnostic. He really didn’t know what to think except that the whole notion of heaven and God and the stories of Christ just seemed too random to be true. They seemed just as fabricated as the many gods of Hinduism or Greek mythology; stories that we told our kids and discussed with our friends as a way to share a common theological language and impart values. He had lost faith that there was any sort of meaning to life long ago.

Looking around, Jerry noticed he woke up sitting in a waiting room of some sort. There were other people in the waiting room, but none of them seemed to be paying much attention to him. There was a mother to his left scolding her children for causing a raucous and to his right was a man about a decade younger than himself dressed in a suit, paying close attention to the headphones in his ears. Across from Jerry, was an elderly man reading the day’s news alongside a companion who was sitting politely with her arms crossed wearing a pleasant and patient smile. The woman vaguely resembled Jerry’s own mother.

As he gazed across the room at the mother figure, she locked eyes with him and nodded politely. Out of her lips came a friendly, “hello.”

Jerry felt comforted by her. He wasn’t sure how to approach the issue that was nagging him at the moment, so he decided to be frank. Jerry leaned forward and asked, “Are you dead, too?”

She chuckled briefly before offering a response, “Oh no, I’m not dead since I was never alive to begin with!” She paused and looked around the room. “No one in this room really exists except for you. We’re simply fabrications to make you feel comfortable with your transition. You seem to be taking it quite well.”

She was right about that. Jerry was calm and deliberate. He reasoned he was probably in shock, but intrigued to learn about his new surroundings. “What are we… I mean… what am I doing here? Am I waiting for someone?”

“Yes, dear,” she responded collectedly, “You’re waiting for you.” She hesitated before elaborating, “Once you’re ready, an assessor will welcome you into his office to go over your life with you.”

Despite the absurdity of the situation, everything seemed to make perfect sense to Jerry. He was waiting in a waiting room until he was done waiting. He looked down and then back up almost immediately as another question surfaced in his mind, “Is the assessor real or a fabrication… like you?”

For a moment, Jerry was worried about offending this lady who had been so helpful and forthcoming with him, but was soothed by her maternal qualities. He left like he could converse with her freely like she was family. He imagined that she was here for this purpose. He thought briefly about contextualizing his question or thanking her for her serenity, but then realized she probably didn’t care because she wasn’t real.

The woman looked towards the door to what was presumably the assessor’s office. The door was metal with a sheet of translucent glass on the top. He hadn’t noticed it before, but Jerry now realized the door was the only one in the waiting room and that there was no other way in or out.

The woman returned her gaze to Jerry and replied, “yes, the assessor is real, but not like you. The assessor is God.”

Jerry tightened up. He was about to meet God himself. Although he never really felt like he had a relationship with God before, there was certainly a lot of hype around the guy. It was like meeting a celebrity who you didn’t really care for, then gloating about it to your friends. If he ever saw his friends again he would definitely gloat.

After a few more minutes pondering and looking around, Jerry decided he was ready. Right as he was about to tell the lady across from him that he was prepared to meet God, the door swung open and a man with a striped tie burst through bellowing, “Jerry! Right on time! Come in, come in!”

Naturally, after a brief acknowledgement to the woman who had helped him, Jerry jumped to his feet to follow the man with the striped tie. As he passed the threshold to the doorway, Jerry inquired, “Are you…?”

“The assessor! Yes! So glad you’ve already heard of me!” The man replied in bursts. The man was pleasant, but not particularly divine. Surely, this wasn’t the person who managed the entire universe.

As if to make small talk, Jerry continued, “So you’re God?”

Immediately and without hesitation the man responded, “Sort of, yes. I am an extension of God. Don’t you know? God is everywhere.” The man funneled Jerry through a corridor of cubicles and offices. He went on, “I am a single manifestation of God. God is busy doing many things right now, but one of those things is being here with you in the form of me. Got it?”

“Oh.” Jerry stopped. The assessor stopped with him. Jerry was confused. “Are we here? Is this your office?”

“If you want it to be!” After only a brief hesitation, the assessor charged into the room that Jerry was standing in front of and sat at the desk. He opened the first drawer and pulled out a big file. “This is your life, Jerry!”

Jerry looked at the file. It looked like some sort of permanent record. Jerry sat in the chair across from the desk.

“I hope you weren’t waiting too long out there,” the assessor commiserated. “Some people are out there for days, weeks, sometimes even years! They get it in their head that there’s another way out of limbo other than forward through the door. It can be hard to come to terms with the death of yourself, you know?”

“I suppose so.” Jerry reflected, but didn’t really empathize. He hadn’t dwelled on death too long. Death was simply a fact of life.

“So what’s going to happen now, Jerry, is that I’m going to go over your history so we can evaluate what sort of person you are.” The assessor in the stripped tie, who was in fact an extension of God, explained. “Then, after we hopefully reach some sort of mutual consensus, we can decide where to place you. Sound good?”

Place me?” Jerry didn’t know how to feel about the ominous process laid out before him. He parsed his words before clarifying, “like heaven or hell?”

“Yes! Precisely! Just like heaven or hell!” The assessor appeared relieved that the conversation was proceeding so smoothly. He opened the folder and started thumbing through the documents.

After sitting there for only a few moments, Jerry began to feel impatient. He decided to inquire further about the process, “Are we going through the whole file today?”

“Oh goodness, no!” The man expressed amusement. “First of all, days don’t exist in the afterlife! Not unless you want them to, anyway. Second, there really aren’t many moments in your life we need to review to determine whether you were a good person: only the highlights. How you treated people you cared for, how you treated people who cared for you, how you treated people you didn’t care for, and how you treated people you didn’t know. Stuff like that. Quite simple, really.”

“Logical.” Jerry didn’t really have a basis for judgment, he was just going with the flow; he just wished the flow would hurry up already. “So I’m to sit here while you read through my file looking for the interesting parts?”

“No, no, not at all!” The assessor seemed enthralled by Jerry’s daft inquisition. “Remember: I’m God! I already know everything! Why would I need to read anything?” He chortled. “I’m simply flipping through these papers for your benefit! You see, it makes the process feel less personal if I’m reading through a file rather than reciting your life to you by memory. That would make an awkward experience much worse! You ready?”

He wasn’t really, but responded that he was.

“Good, good.” God looked down at his records. “So it says here that you and your sister had a pet chinchilla when you were children.”

“Yeah, sure. I think its name was Furball.”

“Yes, Furball. I see it here.” The assessor observed as he pointed to a word on a sheet of paper which may or may not have actually said anything on it at all. “It also says that you killed Furball after tossing him in the air and accidentally not catching him. You then went on to try to blame your sister, Emily. Is that correct?”

Jerry reflected on the sore moment in his life before giving a tacit confession.

“You were eight years old.” He looked up to Jerry and gave a stern look before flipping over a few arbitrary pages and continuing, “It appears a few years later, you hadn’t quite learned your lesson. At fourteen, you stood witness to a crowd of boys surround that same sister and tease her because of her crooked nostril. Instead of defending her, you offered the boys your nickname for her, ‘Nosily,’ before walking off with them and leaving her sobbing on the ground. Is that correct?”

Jerry was no longer looking up, but instead had his head buried towards his lap. The guilt of his life was beginning to mount. After several moments of belated aggravation, he owned up to his crime with a solemn nod.

“Emily died a few years back, did she not? Breast cancer.” The man in the tie behind the desk reminder him. “It says here that before she passed away, you apologized for these wrongs as well as many other ways you felt you failed her as a brother when you were younger and then later in life. Is this true?”

Looking back up, Jerry felt vindication. Although he hated thinking on his sister’s death, he did remember fondly how she forgave him for his sins while she was in her final months. He let on a soft smile and nodded again.

“Let’s look at your work life.” God was quick to change the subject. “A lawyer, huh? Don’t see many of those up here…” God looked up, smirked, and exclaimed, “It’s a joke! Lighten up!” Jerry was not in the mood.

“Seems like you defended some pretty controversial clients,” the assessor mused, “Some pretty bad people in here. How did you feel about that?”

Jerry was ready for this line of questioning. He had thought about that moral quandary many times in life and had his response ready to go. “Sir, I believe in the justice system of my country and that everyone has the right to competent counsel. It was never my place to judge right from wrong, only to offer my legal advice to the best of my abilities.”

“Was that your intent when you found a loophole allowing your client to avoid following through on a contractual obligation to donate considerable support to a nearby children’s hospital? It appears that you received special commendation from your colleagues and a sizeable bonus from your client resulting from that discovery.”

“It was an unfortunate result for the hospital, however the mistake was the fault of the regulator who created such a poorly guarded loophole,” Jerry spoke with the same candor and demeanor that he would recount similar cases at professional cocktail parties.

“I see.” God did not seem particularly bought-in to this line of reasoning, but proceeded with his assessment. “After you made partner, it seems you focused on productivity. You convinced the other partners to scratch the company’s pro bono department in favor of focusing more strictly on your bottom line. That included scrapping support for residents facing eviction from low-income housing in favor of doubling the staff defending a multi-national fast food chain. How am I doing?”

“Well…” Jerry replied, “An oversimplification, certainly, but everything you describe was merely a result of the free market. The adjustment in staff resulted in a considerable boost in revenue which, in turn, went back into supporting our community through our increased tax contribution and firm expenses.”

The striped tie assessor paused at this point to roll up his sleeves and clear his throat. He continued, “It was about that time that you took up with a junior associate at the firm. Two years out of law school. That relationship lasted almost four years. You were married to someone else the whole time.”

“Lindsey.” Jerry boasted. He looked across the table and his heart sank. He knew deep down that God was not impressed by his sexual exploits. His mood had turned once more as he attempted to turn the table, “What is this? Why do you care? We both had fun. My wife never found out. No harm done!”

“About Lindsey? No, she didn’t, but how about Molly?”

“Molly?” It took Jerry a moment to recall the name, but once he did, he winced. He knew Molly was a mistake and wished not to be reminded, but knew he would be. So, he preemptively recounted the story, “It was only one time. A waitress. Couldn’t have been much older than twenty. She kept touching my arm as we talked over the wine list. Lindsey did not like us flirting. I told Lindsey I was going home to my wife, but instead I fucked that waitress.” He began to choke up a bit. God awaited patiently as though provoking Jerry to confide further. “I may have led that girl on with a thing, or two, about a place I had in the Bahamas. Gave her a fake number. Never thought I’d see her again.”

“But you did.”

“Yes. I did. She showed up at my place a couple weeks later. Must have found me on the internet. Put a hole in my windshield with a baseball bat. Told my wife everything in the time it took the police to arrive. Lucky for me Molly didn’t know about Lindsey.”

“And Janet, your wife?”

“Oh, she was livid.” Jerry felt as though he’d rather crawl into a hole for the rest of eternity rather than face the demons of his past in order for a chance to get into heaven. “I don’t know how she put up with me. She always suspected I wasn’t faithful. But after that waitress incident, she couldn’t live in the comfortable lie she had set up with herself. At least not with me. Of course, she never told anyone else. She liked being married, you know?”

“Yes, I do. I know everything.” God sure did have a sense of humor despite the burdensome task ahead of him. “I have to say, this is not looking good for you, Jerry. These are not the sorts of things that earn you many favors in the afterlife.”

Jerry was disheveled. The angst that had been beginning to boil up in his stomach crept up his spine and onto his face. He gasped, “Listen, I’ve made some mistakes, but I’m not a bad person!” His frustration was mounting. “Where are the good stories in that file? Pull up something nice about me!”

“I’m trying to stick to the highlights, but I really want this to be a collaborative judgment, so I always encourage my creations to advocate for themselves. What would you describe as your life highlights?”

This wasn’t going how Jerry imagined death. Here he was, at his advanced age, squirming through his life assessment like an intern at a job interview. “I have many highlights! Friends whom I have treated well! And I have donated to many charitable causes!”

“Donations! Excellent!” The man in the tie flipped his papers to reach the bottom of his pile. “Let’s see here, donations for the symphony, an art studio and your undergraduate university. It seems you were so generous that they even had a seat named after you. Very generous, indeed. And smart! Looks like you timed your donations perfectly with the tax year!” The assessment was ripe with sarcasm, which stung Jerry almost to the point of tears. He prided himself on being mentally and emotionally strong, yet he could feel the muscles of his ego being torn to shreds.

“Life is complicated.” Jerry pouted. “It’s not black and white, there are many shades of gray!”

The assessor remained underwhelmed. He allowed for Jerry to finish his rant before interjecting, “If you’re done with your idioms, I actually have a few more highlights to get to…”

He heard no objection.

“I have information here which states you set up a camera in your guest bathroom to spy on female guests in the loo. Is that accurate?”

Jerry didn’t answer.

“I’ll take that as a yes. The next page mentions how you hit a biker with your car on the way home from happy hour one day. Although the biker lay sprawled on the street, you didn’t even pull over the car for fear that you may have your license revoked.” The tie man looked up once more, “Biker was fine by the way. He still has over 30 years left, actually.”

Jerry was hardly paying attention anymore. Words flew by his ears, swirled around his head, and nested firmly into his subconscious.

“…and who could forget the time you opened the gate to your neighbor’s yard and took the collar off his dog while he was at work? Certainly not me! I don’t forget anything!”

That was the last straw. Jerry broke down. But he didn’t cry. He laughed. He began to laugh and laugh.

“Do you think this is funny?” God enquired. “Was it funny when you withheld medication from your dying, senile father because he was becoming too burdensome?

Jerry laughed and laughed. He couldn’t believe that it was all true. God. The afterlife. Heaven and hell. It was all true.

God continued, “How about not telling your wife about the vasectomy? Was your own immaturity enough to justify depriving your wife of the one relationship that may have filled the void that her husband had left her with?”

What were the odds? It defied everything he believed in. It defied science. By all accounts, his meaningless existence should be over.

“You told her that not having kids must have been ‘God’s plan.’ You blamed me! Textbook blasphemy!”

At this point, Jerry put an end to his laughter and simply smiled confidently towards the Lord.

God looked back at him in defiance and asked, “What do you have to smile about?”

Jerry knew why he was smiling. He had found meaning. All the pointless inequality in the world was suddenly anchored by process. An “assessment.” In this unexpected moment, Jerry stared into the eyes of the deity across the table, his eyes filled with tears of fear and joy. He responded:

“Justice.”

 

 

Tumor Immunotherapy Comes of Age: The New Text Book from the Society for the Immunotherapy of Cancer is out!

It was just two years ago when I received a call in my early morning while at was just starting my routing at work in my office in Doha, Qatar. It was from David D’Addona from Demos Medical Publishing: (who knows how he even figure out how to find me there!): “We are interested in publishing something outstanding in your emerging field! What do you suggest?” He said. “What about a Textbook on Cancer Immunotherapy! The field needs it! Too many want to understand the basic principles of immunotherapy as the field is coming of age” Said I.

Well, we did it!!!! Thanks to David and his team! Thanks to Tara Withington (Executive Director) and her  Society for the Immunotherapy of Cancer (SITC ) staff the textbook is out! Thank you to the contributors!!! The  prominent leaders in the field not only took the time to prepare their respective chapter for the textbook, but they did it according to a tight schedule  imposed by the need to produce a contemporary publication!!!!! Thanks to all of you! I am proud and honored to be one of the Editors of this first textbook on Cancer Immunotherapy together with Lisa Butterfield (current President of SITC) and Howard Kaufman (immediate-past President). I thought it, therefore, reasonable, to publish (of course with permission from Demos and SITC) the preface that introduces the book. I want also to recognize the section editors, who accepted to take a big burden working with us toward the timely completion: thank you Tom (Thomas Gajewski), Paolo (Paolo Ascierto) and Raj (Raj Puri). And thank you readers for taking the time to scan over the preface and give us  feed back through this blog or when we will see each other at the Annual Meeting!

 

Text Book Launch

From Left to Right: Howard Kaufman (Immediate Past-President of SITC), Lisa Butterfield (Current President of SITC) and myself (Past-President of SITC) at the SITC exhibit in Chicago – June 2017

 

After a prolonged germination phase, anticancer immunotherapy has blossomed and is producing a plentiful harvest. Just a decade ago, the field consisted of a passionate group of immunologists and a handful of oncologists and surgeons interested in a peculiar phenomenon: the occasional disappearance of advanced cancer in response to immune stimulation. It was reproducible enough to transcend the threshold of anecdotal insignificance and impart sufficient legitimacy to the field to sustain a miniature ecosystem. We were inspired by rare but concrete successes and we pursued the treatment of cancer patients in experimental settings when all other options had failed. There was no need for a textbook then, because we were a selected group of connoisseurs exchanging information at the Annual Meeting of the Society for Immunotherapy of Cancer (SITC, then called the Society for the Biological Therapy) or similar gatherings. And we held a primer at the Annual Meeting to introduce a handful of neophytes to the intricacies of immunologic responses against a tissue that was self and non-self at the same time.

Things have changed recently with rapid developments in terms of scientific understanding and clinical outcomes. The identification of cancer-specific antigens recognized by immune cells and the mechanistic characterization of the interactions that modulate the cross talk between neoplastic and immune cells gave molecular precision to a phenomenological description of cancer regression in mice, and less frequently in humans. The increasing occurrence of clinical responses with the new immunotherapy agents, whether checkpoint inhibitors or adoptively transferred immune effector cells, and the corresponding survival benefit for patients with advanced cancer has awakened the interest of skep- tics, whether scientists, clinicians, or industry partners. Hordes of oncologists, who were never trained in clinical immunology, are embracing this new modality of treatment and they need comprehensive training to deal with the unique pharmacodynamic profile and toxicity management of immunotherapy agents, which are distinct from standard chemotherapy. In addition, a young generation of basic scientists now perceives tumor immunology as a concrete opportunity to pursue a fruitful career

Preface

bridging their knowledge with the tangible opportunity of impacting people’s lives.

Moreover, the ever-growing speed of biomedical discovery relevant to anticancer immunotherapy unrelentingly spawns a wealth of candidate therapeutics needing efficient clinical testing as single agents or in combination. Industry, hampered by the exponentially growing pipeline of candidate products that target not only cancer cells directly, but their interactions with the host’s immune environment, faces, therefore, an unrealistic challenge. Drug development and respective clinical testing need prioritization to optimize patient selection and reduce costs by enhancing the probability of successful outcomes. Nowadays, a wealth of candidate targets, resulting from high-throughput biomedical discovery, exacerbates the demand, particularly when innumerable combinations for the treatment of complex disorders such as cancer are contemplated; thus, the need to identify evidence-based tools for prioritization based on discovery of useful concepts that could feed the development of novel precision-guided therapeutics. At the same time, a strategy to identify useful predictive and surrogate biomarkers is needed. The optimization of evidence-based study design will help manage the extraordinary cost of clinical testing by guiding the selection of optimally informed choices. In association with high- quality prospective correlative studies, this strategy will improve the design of novel, second-generation precision-guided therapeutics. In accord with the rapid development within the field, regulatory and payer agencies also need to keep pace so that more rapid approval of promising drugs and patient access to high-quality delivery of such agents is possible. Finally, the ultimate beneficiaries of these efforts, the patients and their families, are becoming increasingly empowered to make their own choices but they will need guidance and a reference to make the best-informed decisions.

SITC is trying to respond to the exponential growth of educational needs from all these sectors by providing primers at the Annual Meeting, itinerant courses to clinicians throughout the United States (and abroad in the near future), expanding with topical meetings addressing specific questions related to the field, providing practical guidelines for patient management and policy development, and informing on other themes as they emerge through the SITC portal to include as many up- to-date educational activities as possible. In this context, the SITC leadership decided to collate into an authoritative compendium as much information as possible, primarily targeting young basic and clinical investigators but open to all other constituencies.

It made sense that the current presidents of SITC, supported by the SITC staff, should take on the initiative. We tried to include many of them as contributors and we cannot thank them enough for their enthusiastic response. Chapters for textbooks can be painstakingly overbearing, but all contributors managed to complete their part, areas in which they are recognized worldwide as experts, to bring together cutting edge insight that every translational investigator and practicing clinician needs to know about tumor immunology and immunotherapy. The textbook is divided into five sections: Basic Principles of Tumor Immunology, Cancer Immunotherapy Targets and Classes, Immune Function in Cancer Patients, Disease-Specific Treatments and Outcomes, and Regulatory Aspects of Cancer Immunotherapy. Each section has its own introduction and we will not dwell on the details here. Suffice to say that we tried to cover in these sections the continuum from basic principles to practical and clinically relevant information that could allow a critical understanding of the development and testing of novel therapeutics, companion diagnostics, or useful biomarkers, and could inform about the regulatory processes that support safe yet efficient commercialization.

In addition, a chapter on the history of immunotherapy was devoted to the recognition of those who pioneered and championed the field when it did not enjoy the current popularity to provide the reader with a better appreciation of its evolution.

We want to emphasize that the book is not meant to cover all aspects of tumor immunology. Indeed, the field is a compound science that includes two over- lapping disciplines: immunology and cancer biology. Plenty of textbooks cover more basic concepts relevant to each of the two areas, while in this textbook we tried to focus on converging concepts and peculiarities relevant to the relationship between the host and the neo- plastic tissue.

Furthermore, we were concerned about producing a contemporary textbook as close as possible to the cur- rent status of the field. However, considering the rapid evolution of anticancer immunotherapy, particularly in the clinics, it is impossible to claim absolute success: The number of successful clinical trials and corresponding regulatory licensing is growing at an accelerating pace. Thus, this textbook aims at guiding the neophyte through a critical interpretation of upcoming results based on a solid understanding of anticancer immunotherapy concepts within the context of alternative treatments and the potential for their combinations. Because some areas are likely to progress more rapidly than others, we are planning to periodically publish ad hoc updates either as reviews in the SITC official journal—the Journal for the Immunotherapy of Cancer (JITC)—or more formal and detailed chapter updates and new editions through this publisher.

We hope that the readers, especially the young ones, will enjoy this book and find useful information to complement other SITC activities and that they will be inspired to become active members of the tumor immunotherapy community.

I am not Italian!

Moring Fog

Morning Fog at Pillar Point, Harbor El Granada, California – Photo by F. Marincola, May 2017

I’m not Italian!!!!

I moved to the USA in 1981. I was an only child but my parents encouraged me to seek an opportunity at Stanford University. I married an American woman and I had children. It was natural to become American Citizen for them! Well it was at the wrong time.

Nobody bothered to tell me, while I was working at least 16 hours a day in the residency program at Stanford seven days a week that I would lose the Italian Citizenship. There is no excuse for ignorance of the law!!! Even when you are thousand of miles away from your home and you are struggling to survive.That was a new rule initiated by some bureaucrat, who had no idea of what it is to live as an immigrant in another Country.

Well I moved on in my career quite successfully and over and over I was asked while I worked at the National Institutes of Health as a tenured investigator to help my Italian compatriots, which I did with the warmest resolve because we Italians are hard working and smart people who still carry the ingenuity of the Reinassance in our blood.

I helped, and I helped and I helped and one can simply check my records to see how many Italians I helped. I also helped the Italian Embassy in Washington, when they had their “illustrious” politicians visit the NIH, I helped. There is no question then that I was “Italian”.

I had a lot of satisfactions being an Italian abroad! “La fuga dei cervelli!!!” So many times I was asked to help …more and more. We did great things! With Paolo Ascierto, we created “The Melanoma Bridge!” an annual meeting celebrating USA/Italian partnership in cancer research. I wrote a novel celebrating the Southern Italian life-style that received the Corrado Alvaro Award for literature. I was honored with the San Giorgio d’Oro Award as an honorary citizen of my ancestral town in Calabria, I have been granted the honor of being a Professor at my Alma Mater, University of Milan and I give lectures there for free.

…But I am not Italian. Ms Silvia Vandettuoli sent this letter addressed to “Gentile Sig.re Francesco Maria Marincola”. By the way, this woman accused me of being a lier even though she knew nothing about me and she does not know what a life of integrity I lived since I was raised by very strict parents. Who is she?

Ms Italy

…accompanied by a decreed from some guy called Lorenzo Ortona, who happens to believe he has the right to be “Il Console Generale” in San Francisco, only God knows what are his credentials!

Ms Italy 2

Who are these people? Who are they to judge? They could barely polish my shoes! They barely know what it is like to “scendere a salir per altrui scale”. They have no idea about what it was to gain respect in a prestigious place like Stanford University as an immigrant and the NIH afterwards. Do they know what it takes to be a tenured NIH investigator as a foreigner? But I guess I was not a foreigner since “I am not Italian”.

They are talking about “fuga dei cervelli”. I worked so hard to support Italy and mend such imbalances. I collaborated with the top Italian scientists there to help our …I am sorry “your Country” but now I say to all my Italian friends and the 95% of Italian, who are good hard working people. Get out of that place.

Italy does not deserve Italians, only plastic figureheads like Ms Vandettuoli and Mr. Ortona can be part of that “Animal Farm” called Italy.

And of course, I will return my passport! Who cares? I am American and you know what, in spite of Trump, I am proud of t. It is still the best Country in the world! Simply because there are not Ms Vendettuoli or Mr. Ortona here!

Metamorphosis by Anna Loza

Meet my new Pen Pal Anna! She is a Russian writer who loves Chekov just as I do but who can actually read him in his original language! And she is a spectacular biophysicist who works at the NCBI/NIH; check her out! Her real name is Anna Panchenko. This is her first short story translated in English and I have the honor to publish it. Of course, she has her own blog but it is in the formidable Russian language! Please applaud her debut and hopefully expect more to come!

 

Swan

Swan – Photo by Anna Loza

 

 

Metamorphosis

That morning, the nurse did not come. Hope was laying on her bed and listening to the sounds emanating from the stairwell. The neighboring door creaked, and two sets of footsteps echoed from across the tiled floor; one pair of feet shuffled meekly, while the other had a meaningful stride. “It must be the neighbor across the hall”, – Hope thought to herself, before thoughtfully adding – “her son must have come to visit”. The elevator began to rumble and Hope counted to herself – “One, two, three, four”. As if on cue, the elevator stopped on the fourth floor, opening its doors with a metallic bang and slamming shut once more.

Hope looked out the window and saw, as she always did, a small patch of sky and the crown of the birch tree growing near her home. ‘Birchy’, she had lovingly named the tree – it was the only living thing that had never left her side after all these years. Everything else would come and go, each year less frequently than the last. Birds would perch on the windowsill and airplanes would streak across the sky, the low hum of their engines taking Hope to a far-away places she had never been and would never return to. Some years ago, birds had nested in the birch’s crown, and Hope fearfully watched their home sway in the wind. Each time she would helplessly stare, and each time rejoice when the winged parents would return to the nest with worms in their beaks.

Often she would return to memories of her youth – back when she could run, and climb mountains, and swim in the ocean. It was so long ago, yet these sensations seemed far more bright and vivid than her everyday reality – the sensation of wind against her face, the texture of soft, moist soil between her toes, the warmth of a newly-hatched chick resting in her palms. The memories were precise down to the smallest detail: the words spoken, the wrinkles on her mother’s face, the dimples on her daughter’s and every feeling, every single tint. Hope painstakingly preserved her past, not permitting even the smallest memory to wither and die. Often, very often, she would unlock this treasured vault and experience each day anew. Whether sad or joyful, each fragment of the past held a deep importance and she would not let them go. “At least,” she thought, “I’m re- living my own life, not someone else’s”. She had walked this road many times, from end to end, first regretting something, getting angry and repenting, but always coming to the conclusion that

things happened exactly as they should have. She had finally accepted herself fully, from her harsh character to her sudden irritability, her each and every odd whim, and motionless body. She would not change a single thing. Except for one…the death of her daughter.

The disaster occurred unexpectedly, on one of the bright spring days from twelve years ago. It took them all by surprise, freezing the world like a malfunctioning stop-motion picture. The world outside petrified while her insides grew numb with unrelenting pain. Her house became deadly silent. It was not the silence itself that was awful, however – it was the absence of the sonorous chirping of a child. Hope’s daughter had been hit by a car, and soon after the incident paralysis had seized Hope’s body. Her legs were first to go out from the grief, and the rest of her body shortly followed.

As the room sank into twilight, the shadows of the birch tree grew to encompass the opposite wall, the branches trembling and leaves shaking. Hope imagined herself moving with their frenzied dance, yet her body remained in place, yearning for food and water. Down below, the building’s entrance slammed shut over and over as people returned from work, their chatter and laughter drowning out the sounds of the subsiding day. Hope tried to call out the window that had been left open on the previous day, but her voice was too weak, and her feeble call hardly filled the room.

A loaf of black bread sat on the table. Hope tried to take a deep breath, inhaling the pleasant and familiar smell. She succeeded, and conjured up images of eating the bread with a dollop of butter once the nurse returned tomorrow. Hope did not doubt that the nurse would return – Lana came every day, or had at least done so for the past two years. Once Hope’s mother had passed, Lana regularly came to wash and feed the paralyzed woman. Hope had grown attached to her, although she understood that Lana, like many others, would only remain in her life as long as payment was provided. The poor woman had accepted this, as she had learned to do for many things, with submission and humility. She did not complain when Lana began washing and feeding her less frequently and was grateful that Lana still came at all; the nurse was her last thread to the outside world.

This was not the life Hope led before her mother, who had cared for her paralyzed child for over ten years, had passed. Mother would sit with her for many weeks while her daughter mournfully stared at the ceiling; she read books for Hope and sang songs, doting on her child with such warmth and love that Hope occasionally forgot her tragic state. It was Mother who helped Hope accept her immobility and face her depression. Hope’s grief was real, and her sadness melted away the surface layers of her soul, plunging deeper and deeper into its bowels. Hope’s paralyzed body had become a cocoon for the incessant work of the spirit within.

The next day Lana did not return either, and Hope suddenly realized that her nurse would never come again. Ever. The pain and nausea resurfaced, as Hope drowned her body and mind in a sea of self-pity. She had been abandoned, and she was frightened. Like an artifact forgotten in a storeroom gathering dust, or a stray dog left to the mercy of fate, Hope had been forsaken by everyone. She moaned softly and tears started slowly trickling down her lifeless cheeks. No matter how lonely we are, we live among others and can always call out for help, hoping until the end that someone will come. If left to die alone, everything for which you have lived becomes illusory and vain.

Hope closed her eyes and licked her dry lips. She patiently waited, attempting to control her strained nerves. “It’s better to die at peace – to accept the things I can no longer change”, Hope reasoned to herself, but it was in vain. Her soul forcefully protested against the barren path before her, fighting her motionless body. The clock on the opposite wall ticked, the minute hand crawling along the circumference of the timepiece. Each minute grew more painful and dragged on even more as the feelings of hunger were outweighed by a powerful, heated thirst. Evening settled, and Hope considered the strange possibility that it might be more pleasant to die in her sleep. She shuddered at such a likely outcome.

She lay pinned to the bed, as helpless as a dried butterfly specimen in an entomological collection. The woman tried to convince herself there was something, anything that she could do. “I can do this, this time I’ve got it” – she urged herself on, pushing from the depths of her cocoon with incredible effort to try and spread her wings. A slight tremor ran through her body, but it vanished as quickly as it had emerged. Her arms would not move. Her body would not move. “I can, I can,

I can” was the only thought ringing through her brain, blaring over the feelings of hunger and thirst.

Hope awoke suddenly, screaming in horror as she felt a pair of clammy hands upon her forehead. In the panic and disarray, she could not understand to whom these hands belonged. She lay there, as she had always done, with bated breath. As the terror subsided, she realized. These were not the hands of death. These were her hands. They belonged to her.Met

Where is Franco?

Thank those who have been worrying about me: “what happened to Franco? No action in the blog since he moved to Half Moon Bay, California! Was he swallowed by a great white shark? Or kidnapped by a king wave of the big Pacific Ocean at Mavericks Beach?” Thanks for caring; …even for missing my later rambling blogs with their contorted points and counterpoints.

I am well, thank you! Just quite busy in the new job focusing on my main scientific interest: “Why only a minority of patients with advanced cancer benefit and can be cured by stimulating their immune response?” Together with other recent Presidents of the Society for the Immunotherapy of Cancer, I have been editing the first textbook on Cancer Immunotherapy:  which will be hopefully introduced this June in the occasion of the Annual Meeting of the American Society of Clinical Oncology.

I have been establishing my little but enthusiastic group of bioinformaticians, who are set to “crack the code of cancer immune responsiveness“. In other words, I am back to the old Franco, who is enjoying science rather than management …and I love it.

But I did not forget literature! In fact, I am completing the edition of the short stories published in this blog including those from my son Jamie and those from Catterina Coha. The goal is to publish all in a collection entitled: “Cat behind a window” as for the corresponding blog.

And of course, I did not forget about our friend Luca and the “Old Boys Academy“. I am working on the follow up. As a teaser I am sharing  the first paragraph of the next chapter: “The strange case of Clara’s eyes” in which chapter our beloved Luca will have a change to rebuff in person criticisms about his conducts voiced by some concerned comments of yours!

Slide1

Where is Franco? – Modified from the original TDI comic: “Where is Waldo?

 

Teaser from Chapter four, in continuation of A walk in the park, The Old Boys Academy and Sabrina

 

The strange case of Clara’s eyes

 “In the solitude I observe my own image reflected by thousand of mirrors. I am chased by the squander of anonymity while above, staring at me, hover smiling Clara’s eyes. She was an angel who lasted a day, just like a dragonfly. Yet, in those moments, so many of hers transpired; I observed multiplicities of smiles, hints of cries, myriads of misgivings and hesitations …and of hopes and joys …and of sorrows all reflected, like stars in the sky, by the depth of her eternal eyes.”

Thus was Luca explaining to the interlocutor at the “White Truffle Bar” in Corso Venezia…