JITC Digest January 2017

Inside this Issue:

Letter from the Editor

Dear JITC Readers:

As we ring in a new year, the first 2017 issue of the Journal for ImmunoTherapy of Cancer (JITC) features several new articles providing a range of perspectives on cancer immunotherapy. Among the articles, two stand to be highlighted. The first reports the results of a study evaluating whether tumor irradiation augments the immune response to MUC1 tumor antigen. The second is a mini-review examining tumor-related endoplasmic reticulum (ER) stress, the immunosuppressive unfolded protein response (UPR) signaling pathway, and pharmacological approaches to overcome these barriers and enhance the efficacy of cancer immunotherapies.

In “Radiotherapy and MVA-MUC1-IL-2 vaccine act synergistically for inducing specific immunity to MUC-1 tumor antigen”, Hillman et al. share results from a study investigating the effects of a MVA-MUC1-IL-2 cancer vaccine, Transgene TG4010, in combination with radiotherapy, on murine renal adenocarcinoma (Renca) cells transfected with MUC1. Their findings show that only MVA-MUC1-IL-2 combined with tumor irradiation results in complete response and development of specific antitumor immunity. The authors also conclude that administering the vaccine prior to radiation is more effective than administering radiation first. This is valuable information for the design of future strategies combining novel immunotherapies and standard-of-care therapies.

The review from Cubillos-Riuz, Mohamed and Rodriguez entitled, “Unfolding anti-tumor immunity: ER stress responses sculpt tolerogenic myeloid cells in cancer” explores how ER stress leads to activation of an immunosuppressive cellular survival strategy that includes the UPR signaling pathway, in tumor cells and myeloid cells. The authors address the role of UPR mediators in tumor growth and spread, and discuss pharmacological approaches to enhance the efficacy of cancer immunotherapies by reprogramming tumor-infiltrating myeloid cells, a novel concept that is gaining ground as the field explores the many connections between ER stress, autophagy, apoptosis and immune responses.

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

Case Report

Interstitial nephritis in melanoma patients secondary to PD-1 checkpoint inhibitor

Julia Escandon, Stephanie Peacock, Asaad Trabolsi, David B. Thomas, Ayman Layka and Jose Lutzky
Journal for ImmunoTherapy of Cancer 2017, 5:3 (17 January 2017)

From the Authors

"This report describes the clinical presentation and outcomes of two patients on anti-PD1 antibody therapy who developed interstitial nephritis and acute renal insufficiency. The publication of these cases and their different presenting characteristics and timing are intended to raise awareness of this potential complication of immunotherapy."

Jose Lutzky, MD, FACP — Mount Sinai Medical Center

Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma

Kathryn E. Beckermann, Pradeep C. Jolly, Ju Y. Kim, Jennifer Bordeaux, Igor Puzanov, W. Kimryn Rathmell and Douglas B. Johnson
Journal for ImmunoTherapy of Cancer 2017, 5:1 (17 January 2017)

From the Authors

"Metastatic renal medullary carcinoma is a rare but highly aggressive disease that usually occurs in young patients. Here we report a case of an excellent clinical response to nivolumab, and immunologic correlates of the pre-treatment tumor, characterized by vigorous T cell infiltration and PD-L1 expression."

Douglas B. Johnson, MD, MSCI — Vanderbilt-Ingram Cancer Center

Commentary

Potassium channels of T lymphocytes take center stage in the fight against cancer

Laura Conforti
Journal for ImmunoTherapy of Cancer 2017, 5:2 (17 January 2017)

From the Author

"Potassium channels regulate multiple functions of human T lymphocytes including cytotoxicity, cytokine release, migration and proliferation. Recent reports indicate that they play a role in immune surveillance in cancer and are potential new targets for improving the activity of effector T lymphocytes in the tumor microenvironment."

Laura Conforti, PhD — University of Cincinnati

It's a long way to the top (if you want to personalize immunotherapy)

Sarah Häbe and Oliver Weigert
Journal for ImmunoTherapy of Cancer 2017, 5:6 (17 January 2017)

From the Authors

"Follicular lymphoma (FL) is among the most common lymphomas worldwide and remains incurable for most patients. Considered to be an immunogenic disease, various immunotherapeutic approaches hold promise to be game-changers. We discuss recent advances as well as the challenges of personalizing immunotherapy for FL."

Oliver Weigert, MD — Ludwig Maximilian University of Munich

Research Article

Radiotherapy and MVA-MUC1-IL-2 vaccine act synergistically for inducing specific immunity to MUC-1 tumor antigen

Gilda G. Hillman, Lyndsey A. Reich, Shoshana E. Rothstein, Lisa M. Abernathy, Matthew D. Fountain, Kali Hankerd, Christopher K. Yunker, Joseph T. Rakowski, Eric Quemeneur and Philippe Slos
Journal for ImmunoTherapy of Cancer 2017, 5:4 (17 January 2017)

From the Authors

"The combination of radiotherapy and immunotherapy for cancer has generated renewed interest and excitement, with numerous preclinical and clinical studies during the past 10 years. Mechanistic studies emphasized the role of radiation for inducing immune modulation in the tumor microenvironment, including inflammatory responses, destruction of tumor cells, disruption of stroma and vasculature, which enhanced the efficacy of immunotherapy. Our current pre-clinical study showed that a viral MVA-MUC1-IL-2 cancer vaccine synergized with tumor irradiation leading to curative antitumor responses and specific antitumor immunity to MUC1 antigen, which were not achieved with either modality alone."

Gilda G. Hillman, PhD — Karmanos Cancer Institute and Wayne State University

Review

Unfolding anti-tumor immunity: ER stress responses sculpt tolerogenic myeloid cells in cancer

Juan R. Cubillos-Ruiz, Eslam Mohamed and Paulo C. Rodriguez
Journal for ImmunoTherapy of Cancer 2017, 5:5 (17 January 2017)

From the Authors

"ER stress responses promote malignant progression by operating directly on the cancer cell. Recent findings now indicate that ER stress also influences the function of myeloid cells in the tumor microenvironment."

Juan R. Cubillos-Ruiz, PhD — Weill Cornell Medical College

December Highly Accessed Articles

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma

Douglas G. McNeel, Neil H. Bander, Tomasz M. Beer, Charles G. Drake, Lawrence Fong, Stacey Harrelson, Philip W. Kantoff, Ravi A. Madan, William K. Oh, David J. Peace, Daniel P. Petrylak, Hank Porterfield, Oliver Sartor, Neal D. Shore, Susan F. Slovin, Mark N. Stein, Johannes Vieweg and James L. Gulley
Journal for ImmunoTherapy of Cancer 2016 4:92 (20 December 2016)

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia

Michael Boyiadzis, Michael R. Bishop, Rafat Abonour, Kenneth C. Anderson, Stephen M. Ansell, David Avigan, Lisa Barbarotta, Austin John Barrett, Koen Van Besien, P. Leif Bergsagel, Ivan Borrello, Joshua Brody, Jill Brufsky, Mitchell Cairo, Ajai Chari, Adam Cohen, Jorge Cortes, Stephen J. Forman, Jonathan W. Friedberg, Ephraim J. Fuchs, Steven D. Gore, Sundar Jagannath, Brad S. Kahl, Justin Kline, James N. Kochenderfer, Larry W. Kwak, Ronald Levy, Marcos de Lima, Mark R. Litzow, Anuj Mahindra, Jeffrey Miller, Nikhil C. Munshi, Robert Z. Orlowski, John M. Pagel, David L. Porter, Stephen J. Russell, Karl Schwartz, Margaret A. Shipp, David Siegel, Richard M. Stone, Martin S. Tallman, John M. Timmerman, Frits Van Rhee, Edmund K. Waller, Ann Welsh, Michael Werner, Peter H. Wiernik and Madhav V. Dhodapkar
Journal for ImmunoTherapy of Cancer 2016 4:90 (20 December 2016)