Letter from the Editor
(1).jpg) Dear JITC Readers:
Despite the many successes of cancer immunotherapy, still a good proportion of patients do not respond to treatment and/or experience toxicities. As a result, there remains a need to identify predictive and prognostic biomarkers that will enhance understanding of the complex interactions between the immune system and cancer and will in turn lead to novel immunotherapies. This month’s issue of JITC features two outstanding Commentaries on this topic.
Dr. Jianda Yuan puts into context a recent article by Darshil T. Jhaveri and colleagues regarding the use of quantitative seroproteomics to identify antibody biomarkers in pancreatic cancer. Dr. Yuan discusses the findings of the article as well as the possible applications of the approach taken by Jhaveri and colleagues to other clinical studies without protein synthesis.
Dr. Leisha Emens, editor of JITC’s Clinical Trials Monitor section, recapitulates the most recent update to the TIME trial published by Elisabeth Quoix and colleagues. This therapeutic vaccination against the MUC-1 antigen in lung cancer patients has provided evidence for a new, relatively simple immune biomarker, predictive of clinical response, based on the assessment of the levels of circulating activated natural killer cells at baseline. In addition, Dr. Emens also updates the current status of simple, predictive biomarkers in cancer immunotherapy.
The tumor microenvironment is rich in immunomodulatory loops implicating tumor cells and a variety of myeloid, stromal and lymphoid cells as well as a plethora of molecules supporting high pitched cross talk between all of these cell types. Nucleotides are a conspicuous part of this molecular vocabulary. ATP, on one hand, released by necrotic cells, is generally strongly proinflammatory and may promote anti-tumor immunity. However, overexpression by cell surface ectonucleotidases CD39 and CD73 in tumors generate adenosine from ATP, on the other hand, which is generally strongly immunosuppressive and may therefore promote tumor growth. In this issue, Montalban del Barrio and coworkers explore the effects of adenosine on the function of myeloid cells infiltrating ovarian carcinoma, a tumor known to overexpress both CD39 and CD73. Their findings support a growing consensus that CD39/CD73 may be a targetable immune checkpoint for cancer immunotherapy.
With best regards,
Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer
Case Report
From the Authors
"Cancer treatment with immune-checkpoint inhibitors is frequently associated with the occurrence of dermatological toxicities. A timely classification into harmless or life-threatening events is needed to consider interruption of immunotherapy and introduction of immunosuppressive agents. In this report of Grover's-like drug eruption, we raise awareness for uncommon immune-related dermatological toxicities and extend the characterization of ipilimumab-induced acantholytic dermatosis."
Viktor Koelzer, MD — Institute of Pathology, University of Bern
Clinical Trials Monitor
From the Authors
"Considerable effort has been invested to develop quantifiable, reproducible PD-L1 assays to predict which patients should receive PD-1 pathway inhibitor, however it is clear that PD-L1 expression by immunohistochemistry is not unequivocol but rather a useful guide to patient selection. It is anticipated going forward that we will employ multiple “lenses” in concert to more definitively identify patients for immune checkpoint inhibitors."
Claud Grigg, MD — Columbia University Medical Center
Commentary
From the Author
"Cancer vaccines can generate tumor-specific T cells and are a critical tool in the cancer immunotherapy armamentarium. The TIME trial is testing an Ankara virus-based vaccine that delivers the tumor antigen mucin-1 and IL-2 in patients with advanced non-small cell lung cancer. Expression of mucin-1 is required in at least 50% of tumor cells for eligibility, and the trial is also evaluating the baseline level of triple positive natural killer cells--TrPAL--as a candidate predictive biomarker of response. This trial illustrates the importance of incorporating the evaluation of biomarkers that can select patients most likely to respond into the development of immune-based cancer therapies."
Leisha A. Emens, MD, PhD — Johns Hopkins University
From the Author
“Recent advances in novel high throughput technologies have helped shed the light on the circulating biomarkers in cancer immunotherapy. Mirroring the temporal interaction between the tumor and immune system within the tumor microenvironment, circulating biomarkers provide real-time monitoring of response and can guide personalized cancer immunotherapy.”
Jianda Yuan, MD, PhD — Merck
Research Articles
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Phase II study of vemurafenib followed by ipilimumab in patients with previously untreated BRAF-mutated metastatic melanoma
Asim Amin, David H. Lawson, April K.S. Salama, Henry B. Koon, Troy Guthrie Jr, Sajeve S. Thomas, Steven J. O’Day, Montaser F. Shaheen, Bin Zhang, Stephen Francis and F. Stephen Hodi
Journal for ImmunoTherapy of Cancer 2016, 4:44 (16 August 2016) |
From the Authors
"Sequencing CTLA-4 inhibitor – Ipilimumab after exposure to BRAF inhibitor – vemurafinib was safe and did not exhibit excessive toxicity reported earlier with concomitant administration. An overall 30% response was observed in patients progressing after Ipilimumab with reintroduction of vemurafinib suggesting ongoing BRAF inhibitor sensitivity. Sequencing strategies with combination of BRAF plus MEK and CTLA-4 plus PD1 inhibitors are in development."
Asim Amin, MD, PhD — Levine Cancer Institute - Carolinas Medical Center
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A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma
Todd Crocenzi, Benjamin Cottam, Pippa Newell, Ronald F. Wolf, Paul D. Hansen, Chet Hammill, Matthew C. Solhjem, Yue-Yun To, Amy Greathouse, Garth Tormoen, Zeljka Jutric, Kristina Young, Keith S. Bahjat, Michael J. Gough and Marka R. Crittenden
Journal for ImmunoTherapy of Cancer 2016, 4:45 (16 August 2016) |
From the Authors
"Along with other groups, we are actively studying how best to incorporate immunotherapy amongst standard of care conventional cancer therapies. Prolonged lymphocyte loss in chemoradiation therapy has been described in a range of cancers, yet new clinical trials are still being designed that incorporate conventionally fractionated chemoradiation as a partner for immunotherapies targeting T cells. We demonstrate that altering the radiation fractionation in a matched clinical trial avoids loss of T cells and therefore may represent a superior partner for immunotherapy."
Marka R. Crittenden, MD, PhD and Michael J. Gough, PhD — Earle A. Chiles Research Institute
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Adenosine-generating ovarian cancer cells attract myeloid cells which differentiate into adenosine-generating tumor associated macrophages – a self-amplifying, CD39- and CD73-dependent mechanism for tumor immune escape
Itsaso Montalbán del Barrio, Cornelia Penski, Laura Schlahsa, Roland G. Stein, Joachim Diessner, Achim Wöckel, Johannes Dietl, Manfred B. Lutz, Michel Mittelbronn, Jörg Wischhusen and Sebastian F. M. Häusler
Journal for ImmunoTherapy of Cancer 2016, 4:49 (16 August 2016) |
From the Authors
"Based on in vitro and ex vivo analyses of ovarian cancer samples, Montalbán del Barrio et al. show that tumor-derived adenosine attracts myeloid cells towards the tumor microenvironment where they differentiate into tumor-associated macrophages which upregulate CD39 and CD73. As these ectonucleotidases are responsible for the conversion of ATP into adenosine, this may constitute a novel self-amplifying immunosuppressive mechanism which could be therapeutically targeted by inhibiting CD39, CD73 or the A2A adenosine receptor."
Jörg Wischhusen, PhD — University of Wuerzburg
Short Report
From the Authors
"Preclinical studies and single cases from therapy with checkpoint inhibitors (ipilimumab, pembrolizumab, nivolumab) indicate that these agents can induce autoimmune-mediated cardiotoxicity. Here, patients with a variety of checkpoint inhibitor induced cardiotoxic events with manifestations such as heart failure, cardiomyopathy, heart block, myocardial fibrosis and myocarditis are documented. Since these events can be life-threatening, prompt evaluation and adequate management, i.e. including the application of systemic steroids, are essential."
Lucie Heinzerling, MPH — Universitätsklinikum Erlangen
July Highly Accessed Articles
 NLRC5, a promising new entry in tumor immunology
Sonia T. Chelbi and Greta Guarda
Journal for ImmunoTherapy of Cancer 2016 4:39 (19 July 2016)
Cancer immunotherapy trials: Leading a paradigm shift in drug development
Leisha A. Emens, Lisa H. Butterfield, F. Stephen Hodi, Jr., Francesco M. Marincola
and Howard L. Kaufman
Journal for ImmunoTherapy of Cancer 2016 4:42 (19 July 2016)
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Categories
• Basic Tumor Immunology
• Case Reports
• Clinical/Translational Cancer Immunotherapy
• Clinical Trials Monitor
• Commentary/Editorials
• Immunotherapy Biomarkers
• Reviews
JITC Editor-in-Chief
Pedro J. Romero, MD – University of Lausanne
Section Editors
Lisa H. Butterfield, PhD – University of Pittsburgh Cancer Institute
Christian Capitini, MD – University of Wisconsin - Madison
Leisha Emens, MD, PhD – Johns Hopkins University
Bernard A. Fox, PhD – Earle A. Chiles Research Institute, Providence Cancer Center
Thomas F. Gajewski, MD, PhD – University of Chicago
F. Stephen Hodi, Jr., MD – Dana-Farber Cancer Institute
Cornelis J.M. Melief, MD, PhD – ISA Therapeutics BV
Alfred Zippelius, MD – University Hospital Basel
To view the full editorial board, please click here.
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As a thank you to our members, SITC is offering complimentary article processing charges throughout 2016 (a $2,500 USD savings). For your membership code, contact the SITC office at +1 (414) 271-2456.
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