The Sentinel

THE OFFICIAL BLOG OF THE SOCIETY FOR IMMUNOTHERAPY OF CANCER (SITC).

Tuesday, September 20, 2022

LETTER FROM THE EDITOR - SEPTEMBER

Dear JITC Readers,

Welcome to the latest edition of the JITC digest. Our clinical readers are likely still buzzing with excitement over some of the exciting data that was recently presented at the European Society for Medical Oncology (ESMO) Annual Meeting earlier this month. Immunotherapy was certainly the star of the show, with jaw-dropping response rates to neoadjuvant nivolumab plus ipilimumab in colorectal cancer in NICHE-2 and the first randomized phase III trial showing benefit with cell therapy in a solid tumor in M14TIL. 


Our highlighted papers this month are a nice complement to the news from Paris, featuring real-world clinical data and a position paper with implications for contemporary practice, as well as important translational research to set the stage for future immunotherapies. 


Ana Costa and colleagues use single-cell transcriptomics to characterize the tumor microenvironment of neuroblastoma in a clinically relevant murine model as well as samples from human patients, revealing new insights into the myeloid populations involved in suppressing T cell responses. 


In a drug repurposing screen, Laura Schäkel et al identify the approved anaplastic lymphoma kinase (ALK) inhibitor ceritinib as a novel allosteric inhibitor of CD39, which catalyzes the hydrolysis of ATP to AMP in a key first step in establishing adenosine-mediated immunosuppression. An excellent review on CD39 by David Allard, Bertrand Allard, and John Stagg was published in 2020 in JITC’s Immune Checkpoints Beyond PD-1 series. 


Zeynep Eroglu et al demonstrate that adjuvant anti-PD-1 in patients with sentinel lymph node positive melanoma who did not undergo immediate complete lymph node dissection (CLND) offers similar benefits in a retrospective analysis of real-world outcomes as was seen in the registrational trials of adjuvant therapy in which CLND was mandated. 


Finally, a timely position article from Ahmad A Tarhini and colleagues on behalf of the National Cancer Institute Early Drug Development Neoadjuvant Immunotherapy Working Group summarizes the current state of neoadjuvant immunotherapy of solid tumors, offering suggestions for future progress across disease settings.

 

 

Best regards,

 

Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer

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Thursday, August 25, 2022

LETTER FROM THE EDITOR - AUGUST

Dear JITC Readers,

pedro-romero%281%29%281%29_26717.jpg Welcome to the August edition of the JITC Digest. Many of our readers in the northern hemisphere may be using this time to take advantage of the last few weeks of summer before the academic year resumes. Hopefully you are applying sunscreen regularly if you are reading this edition of the digest at the beach or another idyllic locale.

Looking ahead, I’m thrilled to share the launch of JITC’s Peer Review Mentorship Program. You can find more details in this month’s special feature about this exciting new initiative to help train the next generation of reviewers who will help sustain the quality of our journal and the field as a whole for many years to come.

Our article highlights this month draw from the worlds of microbiology and mathematics—illustrating the power of very small biological entities and very big numbers to optimize immunological control of cancer.

Rebecca A Bekker and colleagues offer a hypothesis paper proposing the use of mathematical approaches to conceptualize the effect of various immune and chemotherapies on the tumor immune microenvironment and tailor combination approaches on a per-patient basis.

In characterizing a vaccine strain of Mycobacterium tuberculosis as an intravesical treatment for bladder cancer, Eduardo Moreo et al elucidate the specific bacterial virulence factors and a requirement for host type 1 conventional dendritic cells for antitumor efficacy.

Teresa T Nguyen and colleagues provide preclinical rationale for combination oncolytic virus therapy plus IDO inhibition for the treatment of recurrent glioma.

And finally, the first spatial mapping of the lung cancer microbiota is described by Abigail Wong-Rolle et al, who find bacteria to be enriched in tumor cells with an accompanying upregulation of genes involved in immune exclusion.

I hope you enjoy the articles in this month’s digest and I encourage early career professionals to consider applying to the Peer Review Mentorship Program.

Best wishes,
Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer

Thursday, July 21, 2022

LETTER FROM THE EDITOR - JULY

 Hello JITC Readers,


pedro-romero%281%29%281%29_26717.jpgWelcome to the latest edition of the JITC Digest. This month we are excited to spotlight our new Imaging and Immunotherapy review series, edited by Elisabeth GE de Vries and Lawrence H Schwartz. This timely review series features discussion on novel emerging imaging strategies, innovative approaches to the analysis of conventional modalities such as artificial intelligence and radiomics, and special considerations for radiotherapy, immunotherapy, and imaging. You can read the introductory editorial to the series as well as the first few reviews at the collection page on the JITC site. Check back throughout 2022 for more publications.

Our original research article highlight this month includes four exciting papers that make progress toward overcoming longstanding challenges in our field: eliciting systemic immune responses to local therapy and serum-based biomarkers for tumor response. 

Robert B Rebhun and colleagues report a clinical benefit rate of 39% with minimal systemic toxicity in a first-in-canine phase I clinical trial evaluating inhaled recombinant human IL-15 for the treatment of spontaneous melanoma or osteosarcoma in companion dogs. 

Regression of untreated lesions in murine melanoma models with local injection of a hydrogel carrying a lysate of the bacterial immunotherapy Mycobacterium bovis Bacillus Calmette-Guérin is described by Mirela Kremenovic et al.

An almost 80% overall response rate to checkpoint blockade in pancreatic ductal adenocarcinoma identified as microsatellite instability-high through ctDNA analysis is observed in a retrospective analysis by Sakti Chakrabarti and colleagues. 

Michal Harel et al leverage machine learning and longitudinal plasma proteomic profiling to identify a signature based on age, sex, and on-treatment serum levels of CXCL18 and CXCL10 to predict benefit with anti-PD-1 in non-small cell lung cancer. 

If you’re looking for more reading material, this month’s selections from JITC’s archives include some of the top case reports and commentary/editorials over the years.


Best wishes,
Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer

Wednesday, June 15, 2022

LETTER FROM THE EDITOR - JUNE

Hello JITC Readers,

pedro-romero_1__1_.jpg

June is always a special month for the journal and our field as we celebrate the 10th annual Cancer Immunotherapy Month™. It’s exciting to mark this month during a time when awareness about and optimism for immunotherapy are at an all-time high after the recent exciting presentation of a 100% clinical complete response rate in a small cohort of patients with mismatch repair deficient locally advanced rectal cancer. 

Of course, the results of such attention-grabbing small studies require extensive efforts from the basic, translational, and clinical research communities before they can become incorporated into the standard of care—and you, our JITC readers, have been instrumental all along the way in helping immunotherapy offer improved outcomes to patients with cancer. Be sure to investigate the offerings in this month’s special feature focused on the position articles and guidelines published in JITC for detailed examples of how the journal provides guidance to enhance decision-making in the immunotherapy field.

Position articles and guidelines are built upon basic and translational advances and the articles selected in this month’s highlight exemplify emerging areas within our field that may set the stage for the next practice-changing developments.

A pair of papers focused on tumor metabolism identify a potential biomarker for benefit and a potential target for drug development. Koichi Azuma et al describe a pre-treatment serum signature of soluble amino acids that predicts benefit with anti-PD-1 monotherapy for non-small cell lung cancer while Apple Hui Min Tay et al synthesize novel antagonists of adenosine metabolism that alleviate suppression of lymphocyte proliferation and effector function in patient-derived tumor spheroid models.

Two papers offer tangible steps toward addressing important unmet needs. Clinical evidence for activity of anti-PD-1 against cancer of unknown primary is reported by Kanwal P. Raghav et al and a novel and pharmacologically targetable tumor-cell intrinsic resistance mechanism to T cell-secreted tumor necrosis factor alpha is revealed by Antonio Sorrentino and colleagues.

I hope you will join us in celebrating Cancer Immunotherapy Month™ and continuing the excitement for the journal’s 10th anniversary year. If you are on social media, be sure to follow @jitcancer and @sitcancer for more exciting offerings throughout the month. 

Best wishes,

Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer

Friday, May 27, 2022

Letter from the Editor - May

Hello JITC Readers,

pedro-romero_1__1_.jpgThis month’s JITC digest marks the beginning of the journal’s 10th anniversary year. Since our first issue was published in May of 2013, the journal and the immunotherapy field have evolved tremendously and we are excited to continue supporting the advancement of the immuno-oncology discipline for many years to come. 


We hope you will join us in celebrating a decade of JITC. Take a walk down memory lane with us by exploring the special features on our 10th anniversary page, including an editorial looking back on the journal’s storied history as well as an illuminating fireside chat between SITC President Dr. Patrick Hwu and JITC leadership on the journal’s trajectory. 


Throughout the past 10 years, JITC has published innovative research from across the immunotherapy field. This month, the papers highlighted in the digest emphasize how even such a familiar topic as PD-1 blockade still yields novel insights with clinical and translational data on novel combination strategies, biomarkers, and response dynamics. 


Acceptable safety with response rates of around 35% are reported by Charu Aggarwal et al in a phase I/II trial evaluating the combination of anti-PD-1 and anti-B7-H3 in checkpoint inhibitor-naïve head and neck and non-small cell lung cancers.  


Yongxiang Xia and colleagues describe efficacy and safety for perioperative anti-PD-1 plus anti-VEGF TKI for hepatocellular carcinoma as well as ctDNA-based biomarkers for predicting response and recurrence risk with the combination.  


An inverse association between somatic copy number alteration burden, immune cell infiltration, and progression-free survival in non-small cell lung cancer is revealed by Joan Frigola and colleagues.  


Finally, Yoon-Koo Kang et al find no evidence for hyperprogression in patients with gastric cancer or small-cell lung cancer treated with checkpoint blockade in the first analysis of the phenomenon using data from randomized controlled trials.  


No matter whether you’ve been with us from the beginning or have just recently discovered JITC, we’re grateful for all our readers and we’re excited for what the future has in store for the journal and our field. 

Best, 


Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer