JITC Letter From the Editor -October 2020

Dear JITC Readers,

Welcome to the latest edition of the JITC digest. For many of our readers, especially in the United States, October is associated with Halloween—the seasonal mood hearkens back to the earliest days of immunotherapy, when many considered the concept of immunological control of tumors to be the stuff of “witchcraft.”

Now, of course, thanks to tireless efforts by clinicians and researchers as well as participation by patients in clinical trials, our understanding of tumor immunology has advanced by leaps and bounds. Concepts once thought to be spooky and mysterious such as immune checkpoints are now generally accepted as common knowledge. Every advance, however, also brings new areas of inquiry, and JITC will continue to publish the leading research in our field. The JITC’s corrected Impact Factor just released by Clarivate Analytics of 10.252 attests to the growing influence of the journal in a field that has taken center stage in oncology and immunology.

We also look forward to SITC’s annual meeting and pre-conference program, this year reimagined as an entirely virtual experience. The virtual meeting will be a one of a kind opportunity to hear from luminaries in our field as well as view presentations on the latest research. Find out more about registration here.

The original research articles featured in this month’s digest highlight several exciting emerging areas in immunotherapy. Elham Beyranvand Nejad and colleagues add a new angle into the important topic of mechanisms of immunotherapy resistance, with an in-depth characterization of the importance of the myeloid cellular component in the tumor microenvironment for preventing recurrence.

Efficient targeting of regulatory T cells in the tumor microenvironment has had limited success to date, but Francesca Zammarchi et al provide promising pre-clinical evidence that a CD25-directed antibody-drug conjugate may efficiently deplete immunosuppressive cells and strongly synergize with checkpoint inhibitors, allowing for robust disease control.

In an outside-of-the-box approach to improve yields for chimeric antigen receptor T cell manufacturing, Andrea Schmidts and colleagues developed artificial antigen presenting cells that improve over conventional bead-based reagents for T cell activation in several aspects. Of note, Schmidts et al modified the artificial antigen-presenting cells to disrupt expression of the lentiviral binding receptor and avoid “vector sink” during transduction using CRISPR-Cas9—the technology honored with the 2020 Nobel Prize in chemistry.

Immunotherapy in the neoadjuvant setting is an important and ongoing area of research. Although the trial of nivolumab and ipilimumab prior to surgery for resectable non-small cell lung cancer reported by Joshua E Reuss and colleagues was prematurely terminated due to toxicity, the findings underscore the importance of future research, especially on biomarkers to predict response to treatment.

Finally, in addition to the excellent original research in this month’s digest, it’s a pleasure to spotlight a review from the recently completed series on immune checkpoints beyond PD-1. If you have not read these outstanding reviews, be sure to browse the entire collection, in addition to the overview of TIGIT in immunotherapy highlighted in this month’s digest.

 

Warm regards,

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

To view the entire September 2020 JITC Digest, please click here. 

JITC Letter From the Editor - August 2020

Dear JITC Readers,

Welcome to this latest edition of the JITC digest. The papers highlighted this month offer exciting perspectives on the current state of the immunotherapy field as well as promising future directions for research.

 

Clinical oncologists can find a comprehensive overview of approved and emerging immunotherapies for multiple myeloma, including some of the new CAR T cell therapies currently in development, in the newest clinical practice guideline from SITC, by Nina Shah et al.

 

Promising clinical data on the use of checkpoint blockade for prostate cancer is provided in an original research article by Julie N Graff et al. The paper is the first to demonstrate durable responses with PD-1 inhibition in a subset of prostate cancer patients.

 

The identification of biomarkers to predict response to immunotherapy remains an important and ongoing area of study for our field. Two papers in this month’s digest highlight the key role that tumor metabolism plays in determining outcomes after immunotherapy, offering potential biomarkers for future study.

 

David Chardin and colleagues identify tumor metabolic parameters as measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) that are prognostic and predictive for outcomes after anti-PD-1 therapy for non-small cell lung cancer. Another immunometabolic biomarker is identified by Fangming Liu et al, who identify an association between FABP5-positive tumor infiltrating T cells and improved overall and recurrence-free survival in hepatocellular carcinoma.

 

New immunotherapeutic targets is another high-priority topic for research, and Marta Trüb and colleagues demonstrate promising in vitro anti-tumor properties with a novel fibroblast activation protein (FAP)-targeted 4-1BB agonist (FAP-4-1BBL).

 

Finally, do not miss an excellent review by Christopher A Chuckran et al of Neuropilin-1, which acts as a receptor ‘hub’ for sorting signals from diverse ligands to both promote regulatory T cell (Treg) stability in the tumor microenvironment and inhibit anti-tumor CD8+ T cell responses—the latest in the Immune Checkpoints Beyond PD-1 review series.

 

As always, you can also further your reading with highlights from other journals in JITC’s Reading List, selected this month by Claudia M Palena, PhD, of the NCI.

Best regards,

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

To view the entire August 2020 JITC Digest, please click here. 

JITC Letter From the Editor - July 2020

Dear JITC Readers,

I am thrilled to share exciting news with you in this latest edition of the JITC digest. This year, JITC increased its impact factor to 9.913, making the journal the highest ranked fully open access immunology journal and in the top 8 percent of all journals in the oncology and immunology categories. The ranking not only reflects the increasing prominence of the cancer immunotherapy field as a whole, but also the outstanding efforts of our JITC editors and expert reviewers, who work tirelessly to ensure that the journal publishes only the top-tier submissions month after month. With a sharp increase in manuscripts submitted to JITC during the last two years, we remain committed to a high standard of timely peer review and to facilitating the publishing of high quality content for our readership.

This month is no exception, with a total of 63 articles publishing in JITC during June. As always, the research spans a wide diversity of topics representing almost every step in the path from bench to bedside. The papers highlighted in this month’s digest include basic research, translational science and human trials.

On the basic science side, Lorena Carmona Rodríguez and colleagues uncover a novel, cell context-specific role for WNT signaling in controlling access to tumors by infiltrating lymphocytes. In another study investigating changes to the tumor microenvironment, Simon P Keam et al demonstrate through NanoString immune gene expression profiling, digital spatial profiling, and high-throughput immune cell multiplex immunohistochemistry analysis on samples from human patients, that high dose-rate brachytherapy converts immunologically cold tumors to hot.

On the therapeutics side, Matteo Libero Baroni et al provide evidence that CD123-directed chimeric antigen receptor T cells are profoundly myeloablative, opening the door to a potential bridge to transplant therapy for acute myeloid leukemia. Victoria A Brentvile and colleagues develop a novel tumor vaccine based on a mixture of three citrullinated peptides that takes advantage of a toll-like receptor agonist adjuvant to dramatically reduce the effective therapeutic dose. Additionally, Adi Reches and colleagues identify a potentially promising new target for checkpoint inhibition in Nectin4, which is a TIGIT ligand with highly restricted expression to tumor cells.

Finally, David S Hong and colleagues demonstrate significant increases in tumor-infiltrating CD3+ and CD8+ T cells in patients with advanced solid tumors after treatment with a small-molecule antagonist of the E-type prostanoid receptor 4 in a first-in-human clinical trial.

I hope you enjoy these articles, and all of the excellent papers published this month in JITC. Also, be sure to peruse this month’s JITC's Reading List for a selection of papers of interest from other journals.

Best regards,

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

To view the entire July 2020 JITC Digest, please click here. 

JITC Letter from the Editor - May 2020

Dear JITC Readers,

Welcome to the May edition of the JITC digest—perhaps you share the sentiment that the month of April seemed exceptionally short. Like every other aspect of life, the journal is still adapting to the ‘new normal’ imposed by the COVID-19 pandemic and we are exceptionally grateful to the editors and reviewers who work tirelessly behind the scenes to enable JITC to continue to publish top-quality immunotherapy research even during these exceptional times.

SITC is proud to stand alongside and support our colleagues on the frontlines of the pandemic, and you can read the society editorial advocating for expanded to IL-6-targeting therapies for COVID-19 in the April issue of JITC.

You may notice that the digest is extra-long this month, featuring four original research articles, two reviews and the aforementioned editorial. It is a testament to the dedication of our immunotherapy community, and we’re excited to share these articles with you, our readers.

April saw two reviews publish that are part of the ongoing JITC "Immune Checkpoints Beyond PD-1" review series. Be sure to read a thought-provoking discussion of the increasing reliance on non-conventional trial protocols in immune-oncology by Luca Mazarella et al. as well as fascinating overview of some potential unusual suspects for checkpoint blockade in the innate cells that function to initiate and guide T cell activity from Carla V Rothlin and Sourav Ghosh.

The original research articles in this month’s digest provide important insight into responses to immunotherapy in real-world patients both in terms of basic tumor immunology and evaluable clinical outcomes.

On the clinical side, John Walker and colleagues describe efficacy and safety outcomes from the largest expanded access program to date and the only for an immune checkpoint inhibitor for metastatic Merkel cell carcinoma, including in immunocompromised patients who were excluded from trials. Additionally, Yukihiro Umeda et al. leverage integrated FDG-PET/MRI-based to predict PFS in nivolumab-treated non-small cell lung cancer based on scans after the first dose.

Delving into immunological responses, Houssein Abdul Sater et al. demonstrate that the therapeutic prostate cancer vaccine PROSTVAC induces systemic immune responses and corresponding increases in lymphocyte infiltration around the tumor despite failing to demonstrate survival benefits in randomized trials. Finally, Tatsuya Yoshida and colleagues provide mechanistic underpinnings behind the link with high C-reactive protein (CRP) and poor outcomes through a variety of in vitro assays showing that CRP inhibits T cell proliferation and effector function as well as dendritic cell phenotypes.

Best regards,

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

To view the entire May 2020 JITC Digest, please click here. 

JITC Letter from the Editor - April 2020

Dear JITC Readers,

Even as the COVID-19 pandemic continues to challenge almost all aspects of daily life, JITC remains unwavering in our commitment to publishing the very best that the immunotherapy field has to offer. Although SARS-CoV-2 is radically changing how we as a community care for our patients and conduct our research, you can count on JITC as a constant source for new findings and important insights from across the spectrum of immuno-oncology. 

This month, the JITC digest offers several papers that develop intriguing strategies to boost antitumor immune responses. Jahangir Ahmed and colleagues engineered a replication-competent oncolytic vaccinia virus that delivers IL-12 to the tumor microenvironment, prolonging survival and controlling lung metastases when administered as an adjuvant to surgical excision in mouse models. Modulation of the tumor microenvironment also synergized with checkpoint blockade in a paper by Lucas A. Horn et al., where combined inhibition of TGF-beta and IL-8 signaling attenuated epithelial to mesenchymal transition in models of both breast and lung cancer. Additionally, Yong Li and colleagues revealed a key role in signaling through the innate immune danger-recognition sensor RIG-I in the development of interferon resistance in melanoma tumor-regenerating cells, identifying STAT3 as a potential therapeutic target. 

Also this month, in a paper that will surely prove reassuring, Nicholas Bevins and colleagues rigorously analyzed the impact of different methods of calculating tumor mutational burden and found good correlation between approaches. 

Finally, be sure not to miss an outstanding review by Lorenzo Galluzzi et al. that delivers a thorough overview of immunologic cell death with detailed discussions of the biological mechanisms leading to the establishment of immunologic memory, the available assays to measure key phenomena, and the hurdles to overcome for translation into clinical benefit. 

Best regards,

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

To view the entire April 2020 JITC Digest, please click here. 

JITC Letter from the Editor - March 2020

Dear JITC Readers,

The COVID-19 pandemic is a global emergency of unprecedented scale, placing an incredible burden on the healthcare system in every affected nation. As JITC readers, you are at the forefront of the outbreak, and, on behalf of the journal as well as SITC as a whole, we wholeheartedly offer gratitude for your ongoing efforts while wishing health and safety for you, your families and your patients.

Publication at JITC continues with this March edition of the JITC digest, which spotlights our commitment to publishing high quality scholarly work in a variety of formats. The journal is quickly becoming not only a leading repository of original research papers in the immunotherapy field, but also a go-to source for top-tier reviews and cutting-edge short hypotheses and case reports.   

Original research articles in this month's JITC digest are similar inasmuch as they describe processes for building tools, but they originate from opposite ends of the translational research spectrum. In a fully computational work that performed all experiments in silico with publically available datasets, Jie Sun and colleagues identify a long non-coding RNA signature as an indicator of immune cell infiltration in non-small cell lung cancer that was predictive of patient outcomes and response to checkpoint blockade. The other paper, from Ssu-Hsueh Tseng et al., describes extensive and elegant "wet" lab work to develop and validate a novel genetically induced mouse model of peritoneal metastasis in high-grade serous carcinoma.

Publishing excellent reviews is a priority for the journal, and we're proud this month to feature a comprehensive discussion of adenosinergic signaling in tumor immunosuppression with a focus on the potential of CD39 as a potential target for checkpoint therapy by David Allard, Bertrand Allard and John Stagg. This is part of JITC's growing Immune Checkpoints Beyond PD-1 review series.  

Finally, Esther Lutgens and Tom Seijkens present a hypothesis that checkpoint inhibition could promote the inflammatory processes in the vascular wall that drive atherosclerosis progression—a concept that merits further study.

As JITC continues to grow and thrive, the efforts and insights of the journal's peer reviewers are always appreciated. It's this "behind the scenes" work that ensures JITC remains the leading journal in the immunotherapy field. If you would like to support the journal while also gaining the many benefits of being a peer reviewer, we are welcoming applications, which you may submit through the SITC Volunteer Portal.

Best regards,

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

To view the entire March 2020 JITC Digest, please click here. 

President's Message - February 2019

Dear Colleagues,

As I enter my second month as President of the Society for Immunotherapy of Cancer (SITC), I am energized in our society’s efforts to continue our growth and success into this new year. As we set the stage for the future, I wanted to offer a brief history of SITC for those new to the society, to acknowledge and celebrate our past, all made possible by a dedicated (and growing) family of SITC members.

SITC was originally founded in 1984 by 40 charter members as the Society for Biological Therapy (SBT). At the time, enthusiasm for cancer immunotherapy was driven by investigations of early cancer vaccines, interferons, interleukin-2 and other types of immune modulators. Fundamental discoveries in molecular biology and immunology over the ensuing years provided the foundation for advances in cancer immunobiology, and consequently ushered in the modern era of cancer immunotherapy, which includes transforming therapies such as the immune checkpoint inhibitors and CAR-T cells. Members of our Society were key drivers of many of these advances, in the lab and the clinic, and through critical roles within industry and government.

I attended my first meeting of the society, then SBT, in approximately 1989, and witnessed the rapid advances in understanding the nature of host anti-tumor immunity over the next decade. Based on a growing body of exciting preclinical data, many agents were brought to clinical trials by dedicated researchers, although with limited clinical success. Nevertheless, members of our society remained steadfast in their efforts to develop highly effective cancer immunotherapies. During the SBT 2002 business meeting, members voted to officially change our name to the International Society for Biological Therapy of Cancer (iSBTc). This change was enacted so that our name would reflect our emphasis and concentration on cancer while embracing and valuing our expanding member footprint across the globe. We experienced further change in 2010 when members voted to refresh the name to the Society for Immunotherapy of Cancer, a moniker that captures our focus and expertise.

The field as a whole, and our society more specifically, has come a long way in the past 35 years. Immunotherapy is not only a viable alternative to other treatments, but now in many malignancies, the most important component of treatment for cancer patients. Improved patient response rates and overall outcomes have undoubtedly played a substantial role in our society’s growth and prosperity, particularly in the past seven years. Since 2012, SITC membership has grown more than 300 percent, from 601 members to 2,457 in 2018.

The diversity of our membership has grown over the years and our society adjusted to reflect the change in composition, adding categories of nurses, pharmacists and patient advocates in recent years. In total, SITC maintains eight member categories for professional and personal classification purposes:

• Regular
• Affiliate
• Emeritus
• Nurse and Advanced Practice Provider
• Patient
• Patient Advocate
• Pharmacist
• Student and Scientist-in-Training

Historically and to this day, our regular member category is our most popular, growing to more than 1,600 professionals in the field in 2018, including basic and translational scientists and practicing oncologists. I find it interesting that while the number of regular members has increased by nearly 450 in the past three years, the category’s representation within the overall SITC membership body has actually declined by three percent since 2016. All other member categories – save emeritus, which has remained steady, comprising 18 members – have increased during the same timeframe, suggesting our reach and effect on the greater cancer community continues to grow. It is clear, though, that once a regular member joins SITC, they find a home in our society, as our retention rate among this category is a staggering 88 percent.

While we know that access to discounted registration rates at SITC programs remains a valued member benefit, our members repeatedly tell us that the ultimate rewards of a SITC membership are the indispensable professional relationships built through society involvement. These relationships expand professional networks and set the stage for meaningful collaborations that spark the next advances in the field, all with the same goal of improving patient outcomes.

I appreciate each and every one of our society’s members, many who have already renewed their memberships for the balance of 2019. Continue reading this month’s Immune Monitor to learn more about the value of a SITC membership. If you’re not currently a member, I encourage you to consider becoming a part of the SITC family.

Sincerely,

Mario Sznol, MD
SITC President

President's Message - January 2019

Dear Colleagues,

I am excited and honored to address you in my first monthly message as President of the Society for Immunotherapy of Cancer (SITC). I have enjoyed the past two years as SITC’s Vice President, supporting Lisa H. Butterfield, PhD, SITC’s first female president, during her tenure as leader of our society. Thank you, Dr. Butterfield, for setting a foundation for the increased inclusion, development, and celebration of women in cancer immunotherapy. The society appreciates your continued leadership and commitment to the field and our organization!

As I assume this role on the heels of another successful year for SITC – which includes reaching new marks within our membership and a record-breaking 5,000 attendees at our Annual Meeting & Pre-Conference Programs – I am looking forward to helping continue our society’s tremendous growth. During my tenure as President, I will work to sustain SITC’s commitment as the leading member association in cancer immunotherapy. I will also ensure SITC remains the host to the most important meeting in the field, as we provide a platform for the presentation of phase 1 clinical trial data that provide insight into the future of immuno-oncology.

SITC has many exciting programs and initiatives slated for the next 12 months, all of which seek to improve cancer patient outcomes by advancing the science, development and application of cancer immunotherapy. A more complete listing of these initiatives is provided below, and I would like to highlight a few occurring in the near future.

It is critical for SITC to continue its emphasis in growing the next generation of leaders in cancer immunotherapy and tumor immunology. This is an area I am keenly focused on and support heavily. To that end, SITC is pleased to continue to offer SITC Fellowship Awards in 2019. Made possible through generous support from our industry partners, SITC Fellowships honor some of the brightest young minds in the field. The development and celebration of young investigators in our field is an important strategic priority of the society and one of my foci as President.

Additionally, registrations are open for SITC’s first Cancer Immunotherapy Winter School. Scheduled for Feb. 18-22 in Mesa, Ariz., this new program, tailored to early career scientists and clinicians as well as those new to the field, will teach the fundamentals of cancer immunotherapy and allow attendees to choose from a variety of tracks that focus on topics most relevant to them. Space is limited so register early! Also, SITC will host its first Meet-the-Expert Webinar on Thursday, Jan. 17 at 12:30 p.m. CST. This hour-long webinar, moderated by Sruthi Ravindranathan, PhD (Emory University), and with participation from presenter Vionnie W.C. Yu, PhD (Novartis Institutes for Biomedical Research), will focus on the topic Careers in Industry. Please click here to register for this free online event.

SITC continues its 2018-19 Advances in Cancer Immunotherapy™ (ACI) regional education program series, with events currently confirmed for Sacramento, Calif., on Jan. 10 in Houston on Feb. 9 and in Portland, Ore., on Feb. 21. Also, we look forward to hosting two, back-to-back thoughtful and engaging interim workshops, focused on cancer immune responsiveness and resistance; and adoptive cellular therapy. Stay tuned for information regarding location, registration and lodging.

If you haven’t already, I hope you’ll consider joining or renewing your SITC membership in 2019 to enjoy a variety of member benefits, including early access to register for the 34^th Annual Meeting & Pre-Conference Programs, scheduled for Nov. 6-10, 2019, in National Harbor, Md.

I am excited to strengthen existing, and build new, relationships with leaders in the field as we work together to continue the growth and success of the society.

Sincerely,

Mario Sznol, MD
SITC President