Letter from the Editor
(1).jpg) Dear JITC Readers:
As anti-PD-1/PD-L1 agents continue to further transform the field of cancer care, the October 2016 issue of the JITC Digest features three research articles that shine light on anti-PD-1 immune therapies.
First, following emerging evidence that chemotherapy agents can regulate B7-H1 expression on cancer cells, Gaurav Goel and colleagues evaluate the effect of 5-fluorouracil on PD-L1 expression in colon cancer cell lines in their Clinical/Translational Cancer Immunotherapy article titled “5-Fluorouracil upregulates cell surface B7-H1 (PD-L1) expression in colon cancer cells: a potential mechanism for chemoresistance.” Their findings suggest a promising approach for future research.
Second, the research article titled “PD-1-refractory tumors respond to anti-PD-1 treatment when combined with vaccine driven specific T cell clonal expansion,” by Genevieve Weir, et al., reports on boosting the activity of PD-1 in a PD-1-refractory murine model that has low levels of PD-L1 expression at baseline. Their results indicate an ongoing need to examine therapeutic approaches that combine vaccines and checkpoint inhibition.
Lastly, Bridgette A. Kanz and colleagues take a closer look at clinical trial eligibility for patients who have traditionally been excluded from these opportunities in their retrospective study, “Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction.” Here, they dig deeper to further assess irAEs and exacerbation of organ dysfunction, as well as survival rates and response, in these special patient populations.
Also highlighted in this month’s issue is a review article from Sasha E. Stanton and Mary L. Disis on the “Clinical significance of tumor-infiltrating lymphocytes in breast cancer.” This article examines the prognostic potential of these lymphocytes for breast cancer treatment, and discusses the potential connection between TILs and use of PD-L1 expression as a biomarker.
With best regards,
Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer
Review
From the Authors
"Our article 'Clinical significance of tumor-infiltrating lymphocytes in breast cancer' is a review of the current literature on the importance of tumor-infiltrating lymphocytes (TILs) in breast cancer and how the effect and composition of TILs is affected by breast cancer subtype. However, despite the recent benefits that have been found with lymphocyte-predominant breast cancer (LPBC >50% TILs) in a small subset of triple negative and HER2-positive breast cancer, the majority of breast cancers do not have LPBC. Lack of immune infiltrate may contribute to the modest response to immune checkpoint inhibitor monotherapy that has been seen in breast cancer. Methods to increase tumor immune infiltrate, including certain chemotherapy regimens, monoclonal antibody therapy (including HER2 monoclonal antibodies), treatment with immune checkpoint activation therapies (41BB and OX40) and local therapies including cryotherapy and radiation may be necessary to allow a wider population of breast cancer patients to benefit from targeted immune therapy."
Sasha E. Stanton, MD, PhD — University of Washington
Case Report
From the Authors
"This case report illustrates an unusual but important adverse event attributed to checkpoint blockade. As the use of checkpoint inhibitors expands, we continue to gain knowledge of common and uncommon side effects and their optimal management. Vigilance regarding side effects and collaboration with experts in non-oncology disciplines is essential."
Leslie A. Fecher, MD — University of Michigan
From the Authors
"The programmed-death 1 (PD-1) pathway is not only a key target of cancer immunotherapy, but is also proposed as a key mediator of solid organ transplant tolerance. We present a case where anti-PD-1 treatment resulted in both acute renal allograft rejection and metastatic melanoma regression. We discuss the ‘double-edged sword’ of targeting PD-1 in solid organ transplant recipients, highlighting the dangers, clinical conundrums and avenues for further research in this challenging patient population."
Michael Ong, MD, FRCPC — The Ottawa Hospital Cancer Centre
From the Authors
"There was little in the literature to help us decide how to deal with a metastatic cancer of apparent donor origin in a renal transplantation patient with prior bladder cancer. Based on initial cytogenetics, we presented the tumor board and patient with an unusual approach: no chemotherapy and stop immunosuppression. Molecular analysis later supported the independent origin of the tumors, and at one year the patient has no evidence of disease and plays golf on a regular basis."
Harry A. Drabkin, MD — Medical University of South Carolina
Research Article
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5-Fluorouracil upregulates cell surface B7-H1 (PD-L1) expression in gastrointestinal cancers
Lauren Van Der Kraak, Gaurav Goel, Krishnaveni Ramanan, Christof Kaltenmeier, Lin Zhang, Daniel P. Normolle, Gordon J. Freeman, Daolin Tang, Katie S. Nason, Jon M. Davison, James D. Luketich, Rajeev Dhupar and Michael T. Lotze
Journal for ImmunoTherapy of Cancer 2016, 4:65 (18 October 2016) |
From the Author
"Checkpoints in immunology are the most important recent novel targets in cancer biology and cancer treatment, effective in patients with melanoma, renal cancer, lung cancer, bladder cancer, Hodgkin's Disease and many other tumor types. This article alerts the cancer community to the critical importance of immuno-oncology. Now, it appears, chemotherapy itself can induce resistance to immune mechanisms by up-regulating PD-L1."
Michael T. Lotze, MD — University of Pittsburgh Cancer Institute
From the Author
"Tumor-infiltrating lymphocytes (TIL) were isolated and expanded from human pancreatic tumors and shown to be activated and tumor-reactive. With limited effective treatment options for patients with pancreatic cancer, these data support the development of adoptive cell therapy using TIL."
Amod A. Sarnaik, MD — H. Lee Moffitt Cancer Center & Research Institute
From the Author
"This work explores how the tri-therapy combination of a vaccine, an immune modulating agent and anti-PD-1 enhances antitumor immune responses using a preclinical model that is not responsive to anti-PD-1 monotherapy. Our results show that anti-PD-1 enhances vaccine-induced immune responses by promoting clonal expansion of antigen-specific CD8+ T cells within the tumor microenvironment. This provides support for the use of anti-PD-1 to enhance vaccine therapy in clinical indications where anti-PD-1 monotherapy is not effective."
Genevieve M. Weir, PhD — Immunovaccine
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Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction
Bridgette A. Kanz, Megan H. Pollack, Romany Johnpulle, Igor Puzanov, Leora Horn, Alicia Morgans, Jeffrey A. Sosman, Suthee Rapisuwon, R. Martin Conry, Zeynep Eroglu and Douglas B. Johnson
Journal for ImmunoTherapy of Cancer 2016, 4:60 (18 October 2016) |
From the Author
"Patients with pre-existing organ dysfunction are often excluded from clinical trials of new treatments, including anti-PD-1 based therapies. We observed that anti-PD-1 had manageable toxicities and preserved antitumor activity in a group of patients with dysfunction of the heart, liver and/or kidneys."
Douglas B. Johnson, MD, MSCI — Vanderbilt-Ingram Cancer Center
Meeting Report
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Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge,” Napoli, December 5th 2015
Paolo A. Ascierto, Maria Libera Ascierto, Silvia Formenti, Sacha Gnjatic, Hans Hammers, Vera Hirsh, Rolf Kiessling, Ignacio Melero, Rita Nanda, Graham Pawelec, Sandro Pignata, Pedro Romero, Daniel E. Speiser, Bernard A. Fox and Francesco M. Marincola
Journal for ImmunoTherapy of Cancer 2016, 4:62 (18 October 2016) |
From the Authors
"This is a report from the first 'Immunotherapy Bridge' meeting held in Naples on December 5, 2015. This report describes the most important advances in the field of immunotherapy both in translational and clinical research, with a focus on lung cancer, renal cell cancer, multiple myeloma, breast cancer and ovarian cancer."
Paolo A. Ascierto, MD — Istituto Nazionale Tumori-Fondazione 'G. Pascale'
Short Report
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High-dose interleukin2 – a 10-year single-site experience in the treatment of metastatic renal cell carcinoma: careful selection of patients gives an excellent outcome
S. Chow, V. Galvis, M. Pillai, R. Leach, E. Keene, A. Spencer-Shaw, A. Shablak, J. Shanks, T. Liptrot, F. Thistlethwaite and R. E. Hawkins
Journal for ImmunoTherapy of Cancer 2016, 4:67 (18 October 2016) |
From the Authors
"In this paper, we detailed the outcomes obtained using our selection criteria based on both tumor morphology and clinical features to maximize the therapeutic efficacy of IL2 in patients with metastatic renal cancer. We achieved complete remission, in 22% of patients and in most cases response was very durable. Our results suggest that HD IL2 still has an important place in the treatment of metastatic renal cell carcinoma despite the development of targeted therapy and checkpoint inhibitors, since rates of complete remission remain much lower with these therapies. The role of IL2 in combination with other immunotherapies should also be explored."
Shien Chow, MBChB, MRCP — Christie NHS Foundation Trust, Manchester
September Highly Accessed Articles
 Current clinical trials testing the combination of immunotherapy with radiotherapy
Josephine Kang, Sandra Demaria and Silvia Formenti
Journal for ImmunoTherapy of Cancer 2016 4:51 (20 September 2016)
Adjuvants for peptide-based cancer vaccines
Hiep Khong and Willem W. Overwijk
Journal for ImmunoTherapy of Cancer 2016 4:56 (20 September 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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