Letter From the Editor - June

Hello JITC Readers,

This edition of the JITC Digest is extra special because June is Cancer Immunotherapy Month™. As JITC readers, you are already aware of the transformational impact of immunotherapy and we welcome you to take advantage of the myriad educational growth and professional development opportunities for clinicians, researchers, and patients offered by SITC during June.

 

June has already been a banner month for immunotherapy, especially for our clinical colleagues. Those of you who attended the American Society for Clinical Oncology Annual Meeting just a few weeks ago—or who followed JITC’s Twitter commentary—likely saw the panoply of oral abstracts, posters, plenary addresses, and education sessions all featuring impressive data showing benefit for a variety of immunotherapy approaches across numerous disease settings. If the results of RELATIVITY have you seeking more information on LAG3 or other targets, be sure to revisit JITC’s Immune Checkpoints Beyond PD-1 Series.

 

Of course, the clinical successes of immunotherapy stemmed from years of basic and translational research, more of which is needed to bring about the next generation of therapeutic agents to overcome resistance and expand the population of patients that may benefit. This month’s original research offers insight into mechanisms of resistance to a variety of immunotherapeutic modalities, with intriguing implications for future development.

 

Francisco J Cueto et al uncover paradoxical inhibition of Flt3L-mediated tumor clearance mediated by a surface receptor involved in cross-priming. Improved tumor control in mice with a novel, extended half-life recombinant IL-15 is demonstrated by Takahiro Miyazaki and colleagues. For the first time, hypoxia is shown to mediate anti-PD-1 resistance in head and neck cancer by Dan P Zandberg et al. Finally, Zhiliang Bai and colleagues identify functional differences in CAR T cells generated from healthy donors and patients.

 

After reading this month’s JITC, continue to celebrate Cancer Immunotherapy Month™ by supporting our sister journals in the immunotherapy space. You can find links to other specialized publications aiming to advance the field forward in this month’s special highlights section.

 

Best regards,

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

To view the entire April 2021 JITC Digest, please click here. 

Letter From the Editor - May

Dear JITC Readers,

Welcome to the latest edition of the JITC Digest. Astute readers have likely noticed that this month’s digest is debuting a new feature. In addition to the usual programming—exciting new publications in JITC—the digest will now also highlight popular papers from the journal archive.

 

This month, we have four original research articles that offer novel insight on one of our field’s most challenging obstacles: resistance to therapy. Addressing immunotherapy resistance is a priority for the field as a whole, and the Society for Immunotherapy of Cancer is spearheading efforts toward developing uniform clinical definitions of resistance as well as support the basic and translational research in order to understand and overcome the mechanistic underpinnings.

 

Barbara Manzanares-Martin and colleagues reveal a surprising association between genomic heterozygosity for the killer-cell immunoglobin-like receptor and overcoming KRAS mutation-mediated resistance to cetuximab.

 

Disease that develops resistance to anti-PD-1 therapies is often highly challenging to treat, but results from two early phase trials in this month’s digest may offer patients new options. Brendan D Curti et al show safety and promising efficacy with the combination of a novel galectin antagonist and pembrolizumab for melanoma and head and neck cancer. Intratumoral injection of the oncolytic poliovirus PVSRIPO led to complete regressions even in uninjected lesions in some patients with melanoma in a phase I trial reported by Georgia M Beasley et al.

 

Finally, Michael W Knitz and colleagues provide deep mechanistic characterization of the interplay between dendritic cells and regulatory T cells that causes head and neck cancers to remain stubbornly immunologically cold after radioimmunotherapy.

 

Be sure to browse this month’s highlight of classic papers as well as the new original research—perhaps perspective from the archives may help spark novel insight into a new finding or vice versa.

 

Best regards,

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

To view the entire April 2021 JITC Digest, please click here. 

Letter from the Editor- April

Dear JITC Readers,

It is a pleasure to welcome you to this month’s JITC digest. The original research articles highlighted in this edition are fantastic examples of mechanistic insight interwoven with new strategies for intervention and vice versa—the seamless reverse translational cycle that is central to the immunotherapy field.

 

Novel targets for immunotherapy are characterized by Aiqin Gao and colleagues, who show that blocking ILT4 relieves T cell immunosenescence via ERK-dependent metabolic perturbations, as well as François Anna et al, who take aim at HLA-G with the first chimeric antigen receptor (CAR) T cells against the dual function tumor-specific antigen and immune checkpoint.

 

Esther Redin and colleagues demonstrate that inhibition of the SRC-family kinase YES1 with the approved leukemia drug dasatinib decreases CD4+ Treg conversion and enhances the efficacy of PD-1 blockade in non-small cell lung cancer.

 

Another strategy to augment the anti-tumor effects of PD-1 inhibition is identified by Yoke Seng Lee et al, who establish a link between conventional type 1 dendritic cell counts and responses to immunotherapy in patients with melanoma as well as in a novel humanized mouse model.

Finally, Gino M Dettorre and colleagues validate a readily available index of hyperinflammation incorporating lymphopenia and hypoalbuminemia that predicts outcomes of SARS-CoV-2 infection in patients with cancer—research that hints at interventions to prevent severe disease and nicely complements recently published articles in JITC’s ongoing COVID-19 and Cancer Immunotherapy Review Series.

 

Best regards,

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

To view the entire April 2021 JITC Digest, please click here. 

Letter From the Editor- March

Dear JITC Readers,

Welcome to this month’s edition of the JITC digest. For many of our American and European readers, March marks the one-year anniversary of the first local shelter-in-place orders and travel restrictions in response to the COVID-19 pandemic.

 

Although everyday life is still far from the pre-pandemic normal in many places, it seems as though the news has been increasingly hopeful day-by-day, especially as the pace of vaccination continues to accelerate.

 

We in the immunotherapy community can share in some of the pride in the outstanding success of the RNA-based COVID vaccines—as JITC readers are well aware, the platform was originally developed for anti-tumor therapy. Additional intersections between cancer immunotherapy and SARS-CoV-2 will be explored in JITC’s new COVID-19 and Cancer Immunotherapy Review Series.

 

RNA vaccines are but one of many examples of innovations that originated in the immunotherapy field with far-reaching implications. Our discipline excels at developing new platforms, and there is no shortage of interesting technologies to be found in this month’s original research articles. As an example, be sure to read about the use of virtual clinical trials to optimize dosing schedules for combination oncolytic virus therapy in an intriguing computational biology paper by Adrienne L. Jenner and colleagues.

 

We have a wealth of biomarkers papers this month, all of which not only describe novel observations, but also rigorously provide mechanistic insight into tumor immunobiology. In one such report, Jiakai Hou et al elegantly leverage published data sets combined with a well-designed CRISPR/Cas9 drop-out screen to identify and categorize tumor-intrinsic resistance mechanisms to immune elimination.

 

Retrospective analyses also yield new insights in a paper by SIyuan Dai and colleagues, who identified in silico and validated in vitro a role for CD8+ T cell-secreted CXCL13 in immunoevasion by clear cell renal cell carcinoma.

 

A different chemokine’s receptor, CCR8 is revealed to be a specific marker of intratumoral regulatory T cells and a viable immunotherapeutic target that yields tumor control without autoimmunity in murine models in a manuscript by Helena Van Damme et al.

 

Finally, Karen Slattery and colleagues identify a novel, targetable and prognostic autocrine regulatory circuit involving TGF beta that leads to systemic natural killer cell dysfunction in patients with breast cancer.

 

Although many of us have been physically distanced from each other for much longer than we’d like, it is clear that our community of JITC readers, authors, editors, and reviewers is as strong and vibrant as ever, and I look toward the future with optimism.

 

Best regards,

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

To view the entire March 2021 JITC Digest, please click here. 

Letter From the Editor- February

Dear JITC Readers,

Welcome to the second JITC digest of 2021. The papers highlighted in this month’s spotlight exciting new frontiers in the immunotherapy field—underscoring the advancements made in new therapies beyond checkpoint inhibitors as well as the ever-evolving understanding of how the “classical” treatments exert anti-tumor effects.

 

The journal added new sections devoted to adoptive cell therapies and oncolytic viruses as recently as last year, and these important areas continue to advance.

 

This month, a paper by Jitendra Kumar et al reveals a strategy to overcome a longstanding challenge in adoptive cell therapies for solid tumors, namely, the immunosuppressive milieu in the tumor microenvironment. Additionally, Giulia Marelli and colleagues demonstrate a rational approach to enhancing the efficacy of oncolytic virus therapy with improved systemic distribution and enforced cytokine production for the vector.

 

The central role of the innate immune system in the anti-tumor effects of checkpoint inhibition are increasingly coming to prominence. Highlighting this rapidly evolving avenue of inquiry, Anastasia Prokopi et al provide evidence that dendritic cells are essential for tumor control in melanoma.

 

Complementing the original research in this month’s digest is an outstanding review by Xiuting Liu, Graham D Hogg, and David G DeNardo, which clearly outlines the direct and indirect effects of checkpoint inhibition on non-lymphoid cells. For additional nuanced and sophisticated explorations of the evolving landscape of tumor immune suppression and evasion, be sure to revisit the Immune Checkpoints Beyond PD-1 series.

 

Finally, it would be impossible for JITC to maintain its status as the preeminent immuno-oncology journal without the tireless efforts of anonymous peer reviewers, who ensure that every paper published in the journal is of the highest quality. In 2020, more than 1,400 unique reviewers evaluated papers for the journal, and the editorial board wishes to extend a sincere and heartfelt thank you for their dedication and perseverance. If you are interested in applying to become a reviewer, please visit the volunteer portal to apply.

 

Best regards,

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

To view the entire February 2021 JITC Digest, please click here. 

Letter From the Editor- January

Dear JITC Readers,

Happy new year and welcome to the first JITC digest of 2021. Even against the backdrop of the global COVID-19 pandemic, last year was a banner year for immuno-oncology, with immunotherapy becoming the standard of care in more and more disease settings. I look ahead to 2021 with optimism that the immunotherapy field will continue apace—providing lifesaving options for patients with cancer and advancing our understanding of the basic immunological mechanisms of tumor control.

 

During the month of December, four new papers from the Society for Immunotherapy of Cancer (SITC) were published in JITC, including the clinical practice guideline on immune effector cell-related adverse events, which will be of great value to the hematology and oncology communities. The journal is proud to support the society’s goal of scientific exchange by publishing these excellent peer-reviewed papers among the top-tier research that appears in JITC.

 

The original research articles highlighted in this month’s digest all provide new insight into one of the most challenging questions in our field: Why does checkpoint inhibition induce deep and durable responses in some, but not all, tumors?

 

Joshua R Veatch and colleagues develop an elegant enrichment and deep-sequencing strategy to show that neoantigen-responsive T cells were associated with tumor control in one patient with melanoma—shining light on a relatively minor contribution of self-antigen reactive T cells.

 

Expanding our understanding of potential immune checkpoints beyond PD-1 in virus-associated solid tumors, Isobel Okoye et al identify upregulation of the TIM-3 ligand galectin-9 as a marker of functional exhaustion and impaired T cell and natural killer NK cell responses.

 

The exhaustion phenotypes of T cells from primary and metastatic sites in ovarian cancers are clearly delineated by Galam Leem and colleagues, identifying 4-1BB costimulation as a potential means to reinvigorate defective immune responses in this setting.

 

Finally, in a provocative rebuke of the so-called “obesity paradox,” Shannon K Boi et al show that high body mass index is associated with worse outcomes with PD-1 inhibition for renal cell carcinoma in the real-world setting, and use mouse models to provide mechanistic insight into a role for IL-1 beta in diminished responses to therapy.

 

With best wishes for the coming year,

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

To view the entire January 2021 JITC Digest, please click here. 

Letter From the Editor- December

Dear JITC Readers,

Welcome to the final JITC digest of 2020. You are likely reading this email within a few days of the winter solstice—the shortest day of the year. Although 2020 has been a highly challenging year with some dark and difficult times, it is reassuring to know that each passing day will come with a little more light. 

 

Although the term has by now become cliché, we are indeed living in unprecedented times. Yet looking back upon 2020, some bright spots emerge from the dark and challenging circumstances in which we have been living. The society’s various task forces and working groups published several impactful papers, one of which, by Brian Gastman and colleagues on the SITC Surgery Committee, appears in this month’s issue. SITC also successfully carried out its first ever all-virtual annual meeting, and it was an amazing opportunity to reconnect with colleagues from all over and experience the very best in immunotherapy research (even if our interactions were through videochat windows). 

 

Additionally, JITC increased its impact factor to 10.252 in 2020, making it the highest ranked fully open access immunology journal and in the top 7 percent of all journals published in the oncology and immunology categories. I’m so grateful to you, our JITC readers, for your constant support of the journal, as well as the tireless efforts of all of our editors and peer reviewers. Thank you all so much for helping to make JITC the field-leading journal that it is today.

 

The articles in this month’s JITC digest are exemplary of why the journal continues on an upwards trajectory of success. Not only are the highlighted studies well-designed and tightly controlled, but the results forecast important trends for the future of the immunotherapy field. 

 

Two unique angles on therapeutic vaccination are provided by Juliane Schuhmacher et al and Iuliia Efimova et al, demonstrating that synthetic long peptides and cells dying an iron-dependent death, respectively, may offer advantages for the development of anti-tumor immunity. 

 

Combination regimens including multi-tyrosine kinase inhibitors and checkpoint blockade are the subject of reports by Javier Martin-Broto et al and Kohei Shigeta et al, further establishing the importance of angiogenesis in immune exclusion and demonstrating that combination strategies could expand the number of tumor types susceptible to PD-(L)1-targeting therapies. 

 

Finally, Diana Canals Hernaez and colleagues provide proof of concept that antibodies specific to tumor-restricted glycans can be developed and that they can specifically kill cancer cells when conjugated to toxic payloads.
 
I hope you enjoy this month’s JITC digest, and I wish a sincere and heartfelt happy holidays and best wishes for the New Year!

 

Best,

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- November 2020

Dear JITC Readers,

I hope you enjoy this latest edition of the JITC digest. You are receiving this email after the conclusion of SITC’s 35th anniversary Annual Meeting and Pre-Conference Programs, this year re-imagined as an entirely virtual experience. Although we sorely missed the opportunity to interact with our colleagues in person, the virtual platform was an amazing opportunity for participants from around the world to experience the latest and greatest in immunotherapy research. Hopefully, you had an opportunity to stop by the virtual JITC booth during the meeting!

Included within the highlights of the meeting was the presentation of the annual JITC best paper awards. This year, the manuscripts honored were, “CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma” and “Mechanisms regulating PD-L1 expression on tumor and immune cells.” Of course, the award selection was a difficult decision this year, as JITC is blessed with an abundance of excellent papers, which is truly a “problem” that the journal is lucky to have as we continue to grow and expand.

Among the many important manuscripts published this month is “The Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of acute leukemia,” which is sure to be a valuable resource for the hematology-oncology community.

The rest of the papers in this month’s JITC digest touch on some hot topic areas in immunotherapy—myeloid cells, metabolism and novel targets, among others—inching the field forward to the overall goal of identifying and expanding the population of patients who may benefit, while revealing new insights into the mechanisms of actions of some familiar agents.

Hongfei Wang et al look beyond the traditional T cell-centered view for immuno-oncology and developed a novel myeloid-targeting agent that showed robust synergy with radiation in mouse models.

Blood-based biomarkers for response to checkpoint blockade have long been elusive, but Alissa Keegan and colleagues make use of ultrasensitive single-molecule array technology to identify a familiar cytokine—IL-6—as a potential factor with predictive value for survival benefit after PD-1 blockade.

New nuance in the T cell physiology associated with checkpoint blockade efficacy is provided by Hannah S Newton et al, who perform elegant electrophysiology experiments to identify distinct differences in voltage-gated ion channel activity, calcium flux and chemotaxis in blood- and tumor-infiltrating lymphocytes among patients with pembrolizumab-responsive and non-responsive head and neck cancers.

Potential utility for PI3Kdelta inhibition beyond hematologic malignancies and in solid tumors is demonstrated by Sarah Nicol Lauder and colleagues—intriguingly, they show that combination with anti-LAG3 therapy leads to even more pronounced effects, highlighting the promise of combinatorial approaches for novel immunotherapy targets.

Finally, do not miss an exceptional review by Maria Zagorulya, Ellen Duong and Stefani Spranger, discussing the implications of tissue-specific variability in myeloid cells on the efficacy of checkpoint blockade therapy. 

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. 

President's Message - November 2020

Dear Colleagues,

Only a few days remain before The Society for Immunotherapy of Cancer’s 35^th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020) begins on Nov. 9, 2020. This will be our first virtual meeting, and I anticipate that all the preparation and hard work will produce the best possible meeting experience for our members and our many colleagues who will join us from around the globe. I also want to extend a warm welcome to the more than 1,300 researchers and clinicians who joined the SITC family in 2020 and I look forward to working together with you in the future.

The Annual Meeting is the highlight of the year for our society and there are always many reasons to attend, but the focus is on the new and exciting data from research spanning across the entire spectrum of cancer immunotherapy. Oral and poster presentations will cover a broad range of topics including tumor immunobiology, the tumor microenvironment, mechanisms of response and resistance to immune modulators, novel immunotherapy strategies in the clinic, and emerging clinical data from new agents and combinations.

On behalf of the society, I extend our congratulations to this year’s nominees for the Presidential Award, who will present their work on Friday, Nov. 13, beginning at 1:30 p.m. EST. These abstracts were selected from a large group of submissions and represent the work of highly motivated and talented early career investigators. This year’s nominees are:

• Defne Bayik, PhD – Cleveland Clinic
• Emily Hsiue, MD – Johns Hopkins University
• Nils-Petter Rudqvist, PhD – The University of Texas MD Anderson Cancer Center
• Michal Sheffer, PhD – Dana-Farber Cancer Institute

To mitigate some of the disadvantages of a virtual meeting, opportunities were created within the meeting to enhance connections with presenters. I invite you to attend the virtual poster sessions starting Nov. 9 at 8 a.m. EST hall. In these sessions, attendees can chat in real time with poster presenters during the following designated poster presentation hours:

• Odd-numbered posters: Wednesday, Nov. 11, from 5:15–5:45 p.m. EST, and Friday, Nov. 13, from 4:40–5:10 p.m. EST
• Even-numbered posters: Thursday, Nov. 12, from 4:50–5:20 p.m. EST, and Saturday, Nov. 14, from 1–1:30 p.m. EST

For a complete look at this year’s abstracts, please visit the Journal for ImmunoTherapy of Cancer (JITC), our society’s open access, peer-reviewed online journal, to view the abstract supplement that will be published as a preprint on Monday morning. Also, we extend our congratulations to JITC Editor-in-Chief Pedro J. Romero, MD, and the countless other editors, reviewers and contributors, on the recent news that the journal increased its impact factor to 10.252! This is a remarkable accomplishment in such a short period of time, and Dr. Romero has initiated an ambitious agenda to further increase the value and impact of the Journal.

The SITC Annual Meeting would not be the same without The CheckPoints party, so join in to hear them on Friday, Nov. 13, at 6 p.m. EST (through ZOOM) for a special happy hour. Don’t forget to order your limited edition T-shirt and CheckPoints Mask to support the Forward Fund.

Finally, please remember that everyone registered for SITC 2020 can now explore the SITC 2020 virtual environment. The preview continues prior to the opening of our pre-conference programs on Monday morning. Please click here to set up your profile, access the virtual exhibit hall and plan your schedule for next week.

Thank you all for your commitment to SITC. Look forward to seeing you online next week!

Sincerely, 

Mario Sznol, MD

SITC President

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 Review Series: Immune Checkpoints Beyond PD-1

Checkpoint blockade—therapies that disrupt the interaction between co-inhibitory receptors on T cells and their cognate ligands thereby blunting activation and proliferation despite antigen engagement—is a testament to the power of translational research. What began as a curiosity-driven inquiry into the mechanisms of immune tolerance has blossomed into a fourth pillar of cancer treatment, complementing the traditional triumvirate of chemotherapy, surgery, and radiation to provide remarkable benefits to thousands of patients.   

The discovery of immune checkpoints spurred a renaissance in immuno-oncology, with parallel efforts directed at translating known mechanisms of T cell inhibition into clinically available therapies as well as at the identification of additional targets.

In the past year alone, more than one dozen new approvals were granted in the US for immunotherapies targeting the PD-1/PD-L1 axis. With more than 3,000 active clinical trials evaluating these regimens, not only for advanced or metastatic disease but also in the adjuvant or neoadjuvant settings, the pace of approvals for checkpoint inhibitors is not looking to slow down any time soon.

Despite this unprecedented advancement, a large subset of cancer patients do not respond to PD-1/PD-L1-directed therapies. Additionally, only one approved therapy targets an immune checkpoint other than the PD-1/PD-L1 axis: the anti-CTLA-4 antibody ipilimumab. In recent years, it has become apparent that a panoply of additional signaling pathways modulate T cell activity, with distinct mechanisms outside the role of the PD-1 pathway in controlling ongoing localized inflammatory responses or the function of CTLA-4 in systemic self-tolerance. Some of these newly discovered checkpoints are already the target of numerous investigational agents in human trials and widely considered to be on the cusp of approval, as in the case of LAG-3.

Accumulated experience with the approved checkpoint inhibitors targeting the PD-1 axis has also enabled reverse translational studies that reveal new nuances of the immune landscape of the tumor microenvironment. In addition to the discovery of new co-stimulatory or co-inhibitory receptors and ligands, a prominent role for populations outside the lymphoid lineage has come to light in the activation or suppression of T cell responses, including the importance of innate immune cells and stromal cells for anti-tumor activity. Several of the novel checkpoints that have been discovered in recent years have also been demonstrated to play critical roles in innate-mediated anti-tumor immunity—an important and ongoing area of study for the immunotherapy field. 

Translating observations from pre-clinical models into usable therapies is not without challenges, however, and several investigational agents targeting novel immune checkpoints have, to date, yielded disappointing responses as monotherapies in randomized trials. Yet ongoing studies show hints of promising synergy between existing PD-1/PD-L1-targeting therapies and agents targeting novel checkpoints. Intriguingly, some new agents have demonstrated activity in tumor types generally thought to be weakly immunogenic, suggesting that expanding the repertoire of immune checkpoints could open up new settings amenable to immunotherapy.

Although the clinical development process for novel drugs may seem slow, especially in light of the urgent need for effective therapies for all-too-many still-lethal cancers, checkpoint inhibitors beyond anti-PD-1/PD-L1 agents are poised for a breakthrough. Industry has placed large bets on emerging checkpoints such as LAG-3, TIM-3 and TIGIT, and academia continues to advance the research pipeline.

This review series supports the ongoing momentum for investigation and clinical development of immune checkpoints therapies beyond the PD-1 axis. The articles highlight all aspects of the translational research pipeline—including pre-clinical rationale for novel targets, ongoing human studies, and high-level considerations for trial design. Readers from across the clinical-translational research enterprise will find value in these exceptional reviews. It is an exciting time for immunotherapy, and, with JITC, we are proud to move the field forward in this promising new direction.

Best Regards,

 

Ana Carrizosa Anderson, PhD    
Series Editor                 

                                               

Dario A.A. Vignali, PhD
Series Editor                                                                                                     

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.