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. 

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. 

JITC Letter from the Editor - February 2020

Dear JITC Readers,

Welcome to the February edition of the JITC digest. The journal continues to grow and thrive, publishing impactful research across the entire spectrum of the diverse and interdisciplinary immunotherapy field. The articles in this month's digest highlight innovative approaches to overcoming longstanding challenges in cancer immunotherapy, and will surely spark important conversations moving forward.

I'm thrilled to report that this month's digest features three papers from one of the journal's new sections, Immune cell therapies and immune cell engineering—a burgeoning area that continues to push boundaries in terms of advancing scientific understanding and improving patient outcomes.

The highlighted articles feature somewhat "outside-the-box" cell therapy strategies, two of which could have exciting implications for the treatment of solid tumors. In elegant preclinical models, Rahul Suresh et al. demonstrate robust anti-tumor activity by adoptively transferred gene-edited immature myeloid cells. In a different tactic, the feasibility of generating PD-1-deficient effector memory T cells specific for melanoma antigens was demonstrated by Lucine Marotte and colleagues.

Although cell therapies have a well-established role in the treatment of hematologic malignancies, relapse remains common. In an attempt to improve outcomes, Benjamin Derman et al. demonstrate two effective strategies to significantly reduce and delay T regulatory cell recovery after autologous stem cell transplant in a pilot study of 15 patients with multiple myeloma.

In addition to the exciting articles in the cell therapy section, be sure to read the paper by Shibin Qu et al., describing a novel approach to tumor ablation that causes the release of non-denatured neoantigens and damage-associated molecular patterns capable of potentiating the efficacy of checkpoint blockade for non-immunogenic tumors in mouse models.

Our field keeps moving at a tremendous pace! If you'd like to join in to real-time conversations about the latest research and you're active on social media, be sure to take a moment to follow the official JITC Twitter handle, @jitcancer.  

Best regards,

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

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

JITC Letter from the Editor - January 2020

Dear JITC Readers,

Welcome to the first JITC Digest of 2020! The past decade has seen cancer immunotherapy advance to an incredible degree, and the pace of innovation is not looking to slow down any time soon. It is an exciting time for the field and for the journal as JITC continues to expand and evolve to serve the community.

To support our continued growth, JITC has partnered with a new publisher, BMJ, which will allow the journal to offer an improved experience for authors, editors, reviewers and readers at all steps during the publication process. You can read more about the transition in a special editorial in the January issue.

Additionally, JITC will now offer two new sections focusing on exciting emerging areas in our field: Immune Cell Therapy and Immune Cell Engineering, edited by Dr. Marcela V Maus, and Oncolytic Immunotherapy, edited by Dr. Howard L Kaufman. We’re thrilled to help usher these important and innovative approaches into more widespread clinical use.

The highlighted papers in this month’s digest truly exemplify the tremendous pace of advancement within the cancer immunotherapy field, especially in the area of immune checkpoints. When the journal was first established in 2013, no agents targeting the programmed death (PD)-1 receptor or its ligand had been approved by the FDA and now checkpoint blockade has become a mainstay in the treatment of numerous malignancies.

Kidney cancer is one such disease for which checkpoint blockade has radically altered the treatment landscape, motivating SITC to update its Cancer Immunotherapy Guidelines. You can read the Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma by Brian Rini et al. in this issue.

And our understanding of immune checkpoints continues to progress. Almost every aspect in the translational research pipeline is represented in the manuscripts in this month’s digest, including characterization of the tumor microenvironment, pre-clinical validation for two novel checkpoint blockade strategies, and the first retrospective study of the tolerability of anti-PD-1 or anti-PD-L1 therapy in patients with pre-existing or newly diagnosed paraneoplastic syndromes.

With best regards,

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

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