JITC Digest August 2019

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Inside this Issue:

Letter from the Editor

Dear JITC Readers,pedro-romero_1__1_.jpg

In the August edition of the JITC Digest, I would like to highlight the following articles. First, “The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC),” by Ezra E.W. Cohen et al. details the first new FDA approvals for patients with squamous cell carcinoma of the head and neck (HNSCC) since 2006, including the most recent 2019 approval of pembrolizumab as first-line treatment for patients with metastatic or unresectable, recurrent HNSCC in combination with chemotherapy for all patients or as monotherapy for patients with HNSCC whose tumors express PD-L1. These consensus guidelines serve as a foundation to assist clinicians’ understanding of the role of immunotherapies in this disease setting, and to standardize utilization across the field for patient benefit.

Furthermore, the article, “T cells expressing NKG2D chimeric antigen receptors efficiently eliminate glioblastoma and cancer stem cells” by Dong Yang et al. confirms the high expression of NKG2DLs in human glioblastoma cell lines, CSCs, and tumor samples and provides evidence that NKG2D CAR T cells effectively target glioblastoma cells and CSCs in an NKG2D-dependent manner, thus reporting on an encouraging therapeutic approach for glioblastoma patients.

Next, the research article entitled “Tumor-released autophagosomes induces CD4+ T cell-mediated immunosuppression via a TLR2–IL-6 cascade,” by Yong-Qiang Chen et al. reveals novel cellular and molecular mechanisms of tumor-derived extracellular vesicles in regulating CD4+ effector T cell function and pinpoints tumor cell-released autophagosomes (TRAPs) as a therapeutic target for cancer immunotherapy, specifically reporting HSP90-alpha on the surface of TRAPs as a novel target.

“Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments,” by Shreya Raghavan et al. details the hanging drop spheroid model developed to investigate pro-tumoral macrophage activation in response to CSCs and the role of WNT pathways in CSC-macrophage interactions. Such insight could provide new targets for reducing CSC-burden in ovarian cancer.

“HERA-GITRL activates T cells and promotes anti-tumor efficacy independent of Fc-gamma-R-binding functionality,” by David M. Richards et al. describes the development of a novel agonistic HERA molecule targeting GITR for which the underlying HERA-GITRL structure overcomes significant limitations of bivalent antibody-based approaches by mimicking the natural trimeric ligand, and thus inducing optimal trimeric assembly of the GITR receptors.

Finally, the clinical study, “First-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody, in patients with advanced solid tumors,” by Kohei Shitara et al. reports on single agent IT1208, a humanized anti-CD4 immunoglobulin G1 mAb, which is shown to successfully deplete CD4+ T cells with a manageable safety profile and encouraging preliminary efficacy signals, warranting further investigations, possibly in combination with immune checkpoint inhibitors.

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


JITC Editor Picks

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

Ezra E. W. Cohen, R. Bryan Bell, Carlo B. Bifulco, Barbara Burtness, Maura L. Gillison, Kevin J. Harrington, Quynh-Thu Le, Nancy Y. Lee, Rom Leidner, Rebecca L. Lewis, Lisa Licitra, Hisham Mehanna, Loren K. Mell, Adam Raben, Andrew G. Sikora, Ravindra Uppaluri, Fernanda Whitworth, Dan P. Zandberg & Robert L. Ferris
Journal for ImmunoTherapy of Cancer, 7:184 (15 July 2019)
Position Article and Guidelines

Summary:

Marking the first new approvals for patients with squamous cell carcinoma of the head and neck (HNSCC) since 2006, the FDA first approved the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab for second-line treatment of patients with recurrent disease, then in 2019, granted approval for PD-1 inhibition as first-line treatment of patients with metastatic or unresectable, recurrent HNSCC. This new frontline approval includes pembrolizumab in combination with platinum and fluorouracil for all patients with HNSCC as well as pembrolizumab as a single agent for patients with HNSCC whose tumors express a PD-L1 combined positive score ≥ 1. In order to address questions of patient selection, therapy sequence, response monitoring, adverse event management, and biomarker testing within these novel treatment regimens, Cohen et al. developed this Cancer Immunotherapy Guideline to provide clinicians with evidence-based recommendations and the most up-to-date vision on how immunotherapy can be integrated into the treatment for patients with HNSCC.

T cells expressing NKG2D chimeric antigen receptors efficiently eliminate glioblastoma and cancer stem cells

Dong Yang, Bin Sun, Hongjiu Dai, Wenxuan Li, Lan Shi, Peixian Zhang, Shirong Li & Xudong Zhao
Journal for ImmunoTherapy of Cancer, 7:171 (9 July 2019)
Research

Summary:

Targeted killing of cancer stem cells (CSCs) has been shown to effectively inhibit glioblastoma tumorigenesis and prolong the survival of glioma-bearing mice, overcoming one of the major causes of conventional therapy failure and cancer recurrence for glioblastoma. With recent studies reporting NKG2D ligand (NKG2DL) overexpression in glioblastoma stem cells (GSCs), suggestive of a potential for NKG2D-expressing CAR T cells to elicit a specific effect on GSCs, Yang et al. engineered NKG2D-expressing CAR T cells and investigated their pre-clinical efficacy against human glioblastoma cells and CSCs. This study confirms both the high expression of NKG2DLs in human NKG2D glioblastoma cells and CSCs and indicates that CAR T cells target such cells in an NKG2D-dependent manner, supporting the use of NKG2D-expressing CAR T therapy for glioblastoma patients.

Tumor-released autophagosomes induces CD4+ T cell-mediated immunosuppression via a TLR2–IL-6 cascade

Yong-Qiang Chen, Peng-Cheng Li, Ning Pan, Rong Gao, Zhi-Fa Wen, Tian-Yu Zhang, Fang Huang, Fang-Yuan Wu, Xi-Long Ou, Jin-Ping Zhang, Xue-Jun Zhu, Hong-Ming Hu, Kang Chen, Yun-Lang Cai & Li-Xin Wang
Journal for ImmunoTherapy of Cancer, 7:178 (12 July 2019)
Research

Summary:

Tumor cell-released autophagosomes (TRAPs) are part of an elaborate network of tumor-derived vesicles that can modulate CD4+T cells within the immune response to promote cancer; however, the exact mechanisms behind such immune modulation by TRAPs remains elusive. Chen et al. investigated the mechanistic aspects of TRAPs in the modulation of CD4+ T cells in the tumor microenvironment. This study revealed that TRAPs can redirect CD4+ T cells to promote tumor growth and metastasis through a novel cellular and molecular mechanism which regulates CD4+ effector T cell function, highlighting TRAPs as important therapeutic targets for cancer immunotherapy.

Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments

Shreya Raghavan, Pooja Mehta, Yuying Xie, Yu L. Lei & Geeta Mehta
Journal for ImmunoTherapy of Cancer, 7:190 (19 July 2019)
Research

Summary:

Little is known regarding the specific role of cancer stem cells (CSCs) and their reciprocal interactions with macrophages; however, given the enriched presence of both macrophages and CSCs within the ovarian carcinoma ascites, their interaction might be critical for regulating the progression and drug response of ovarian cancer. In order to dissect this dynamic relationship, Raghaven et al. used a previously established in vitro hanging drop spheroid model to investigate such occurrences. This study successfully models a hetero-spheroid culture system, where ovarian CSCs and activated macrophages are brought together in a 3D, anchorage-independent, in vitro microenvironment, simulating their non-adherent presence within malignant ascites, ultimately linking activation of the WNT pathway by macrophages in ovarian CSCs. Such results have wide-ranging implications for new therapeutic targets to specifically eradicate the immuno-modulation of macrophages by CSCs that contribute to recurrent disease.

HERA-GITRL activates T cells and promotes anti-tumor efficacy independent of Fc-gamma-R-binding functionality

David M. Richards, Viola Marschall, Katharina Billian-Frey, Karl Heinonen, Christian Merz, Mauricio Redondo Müller, Julian P. Sefrin, Matthias Schröder, Jaromir Sykora, Harald Fricke, Oliver Hill, Christian Gieffers & Meinolf Thiemann
Journal for ImmunoTherapy of Cancer, 7:191 (19 July 2019)
Research

Summary:

Glucocorticoid-induced TNFR-related protein (TNFRSF18, GITR, CD357) signaling plays an important role in regulating immune responses by providing co-stimulatory signals to boost T cell activation, differentiation, survival and memory formation and is therefore an especially important target for immunotherapy. While GITR agonists have demonstrated limited clinical efficacy primarily due to the structural and functional characteristics of antibodies, Richards et al. developed a novel agonistic HERA molecule targeting GITR. The novel model described here provides a HERA-GITRL structure which overcomes significant limitations of bivalent antibody-based approaches by mimicking the natural trimeric ligand and inducing optimal trimeric assembly of the GITR receptors. Furthermore, this study reports single agent anti-tumor activity for HERA-GITRL both in vitro and in vivo that should function in combination with immune checkpoint inhibitors.

First-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody, in patients with advanced solid tumors

Kohei Shitara, Satoshi Ueha, Shigeyuki Shichino, Hiroyasu Aoki, Haru Ogiwara, Tetsuya Nakatsura, Toshihiro Suzuki, Manami Shimomura, Toshiaki Yoshikawa, Kayoko Shoda, Shigehisa Kitano, Makiko Yamashita, Takayuki Nakayama, Akihiro Sato, Sakiko Kuroda, Masashi Wakabayashi, Shogo Nomura, Shoji Yokochi, Satoru Ito, Kouji Matsushima & Toshihiko Doi
Journal for ImmunoTherapy of Cancer, 7:195 (24 July 2019)
Research

Summary:

Backed by pre-clinical studies which suggest that depletion of CD4+ cells results in strong antitumor activity due to the enhancement of cytotoxic T-lymphocyte responses, IT1208, a humanized anti-CD4 immunoglobulin G1 mAb, has been shown to markedly enhance antibody-dependent cellular cytotoxicity. In this first-in-human phase 1 study, Shitara et al. demonstrated that IT1208 monotherapy successfully depleted CD4+ T cells in patients with advanced solid tumors with a manageable safety profile and encouraging preliminary efficacy signals, warranting further investigations, especially in combinations with immune checkpoint inhibitors.

Plasmacytoid dendritic cells orchestrate innate and adaptive anti-tumor immunity induced by oncolytic coxsackievirus A21

Louise M. E. Müller, Matthew Holmes, Joanne L. Michael, Gina B. Scott, Emma J. West, Karen J. Scott, Christopher Parrish, Kathryn Hall, Sina Stäble, Victoria A. Jennings, Matthew Cullen, Stewart McConnell, Catherine Langton, Emma L. Tidswell, Darren Shafren, Adel Samson, Kevin J. Harrington, Hardev Pandha, Christy Ralph, Richard J. Kelly, Gordon Cook, Alan A. Melcher & Fiona Errington-Mais
Journal for ImmunoTherapy of Cancer, 7:164 (1 July 2019)
Research

Delayed immune-related events (DIRE) after discontinuation of immunotherapy: diagnostic hazard of autoimmunity at a distance

Marcus A. Couey, R. Bryan Bell, Ashish A. Patel, Meghan C. Romba, Marka R. Crittenden, Brendan D. Curti, Walter J. Urba & Rom S. Leidner
Journal for ImmunoTherapy of Cancer, 7:165 (3 July 2019)
Research

Hypothesis: does adrenalitis caused by immune checkpoint-inhibitors put melanoma patients at an elevated risk for recurrence?

Igor Alexander Harsch
Journal for ImmunoTherapy of Cancer, 7:166 (4 July 2019)
Hypothesis

IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells

Yeon Ho Choi, Eun Jin Lim, Se Wha Kim, Yong Wha Moon, Kyung Soon Park & Hee-Jung An
Journal for ImmunoTherapy of Cancer, 7:168 (5 July 2019)
Research

Isolated neutropenia as a rare but serious adverse event secondary to immune checkpoint inhibition

Abdul Rafeh Naqash, Ebenezer Appah, Li V. Yang, Mahvish Muzaffar, Mona A. Marie, Justin D. Mccallen, Shravanti Macherla, Darla Liles & Paul R. Walker
Journal for ImmunoTherapy of Cancer, 7:169 (5 July 2019)
Case Report

Rescue therapy for patients with anti-PD-1-refractory Merkel cell carcinoma: a multicenter, retrospective case series

Jaclyn LoPiccolo, Megan D. Schollenberger, Sumia Dakhil, Samuel Rosner, Osama Ali, William H. Sharfman, Ann W. Silk, Shailender Bhatia & Evan J. Lipson
Journal for ImmunoTherapy of Cancer, 7:170 (8 July 2019)
Short Report

Tumor regression mediated by oncogene withdrawal or erlotinib stimulates infiltration of inflammatory immune cells in EGFR mutant lung tumors

Deborah Ayeni, Braden Miller, Alexandra Kuhlmann, Ping-Chih Ho, Camila Robles-Oteiza, Mmaserame Gaefele, Stellar Levy, Fernando J. de Miguel, Curtis Perry, Tianxia Guan, Gerald Krystal, William Lockwood, Daniel Zelterman, Robert Homer, Zongzhi Liu, Susan Kaech & Katerina Politi
Journal for ImmunoTherapy of Cancer, 7:172 (10 July 2019)
Research

Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors

Menno Tamminga, Sanne de Wit, T. Jeroen N. Hiltermann, Wim Timens, Ed Schuuring, Leon W. M. M. Terstappen & Harry J. M. Groen
Journal for ImmunoTherapy of Cancer, 7:173 (10 July 2019)
Research

Oncolytic adenovirus drives specific immune response generated by a poly-epitope pDNA vaccine encoding melanoma neoantigens into the tumor site

Alessandra Lopes, Sara Feola, Sophie Ligot, Manlio Fusciello, Gaëlle Vandermeulen, Véronique Préat & Vincenzo Cerullo
Journal for ImmunoTherapy of Cancer, 7:174 (10 July 2019)
Research

Gal9/Tim-3 expression level is higher in AML patients who fail chemotherapy

Paola Dama, Marshall Tang, Noreen Fulton, Justin Kline & Hongtao Liu
Journal for ImmunoTherapy of Cancer, 7:175 (10 July 2019)
Short Report

Role of antibiotic use, plasma citrulline and blood microbiome in advanced non-small cell lung cancer patients treated with nivolumab

Julia Ouaknine Krief, Pierre Helly de Tauriers, Coraline Dumenil, Nathalie Neveux, Jennifer Dumoulin, Violaine Giraud, Sylvie Labrune, Julie Tisserand, Catherine Julie, Jean-François Emile, Thierry Chinet & Etienne Giroux Leprieur
Journal for ImmunoTherapy of Cancer, 7:176 (10 July 2019)
Research

Baseline T cell dysfunction by single cell network profiling in metastatic breast cancer patients

Silvia C. Formenti, Rachael E. Hawtin, Neha Dixit, Erik Evensen, Percy Lee, Judith D. Goldberg, Xiaochun Li, Claire Vanpouille-Box, Dörthe Schaue, William H. McBride & Sandra Demaria
Journal for ImmunoTherapy of Cancer, 7:177 (11 July 2019)
Short Report

Immune cell concentrations among the primary tumor microenvironment in colorectal cancer patients predicted by clinicopathologic characteristics and blood indexes

Guifang Guo, Yixing Wang, Yixin Zhou, Qi Quan, Yijun Zhang, Haohua Wang, Bei Zhang & Liangping Xia
Journal for ImmunoTherapy of Cancer, 7:179 (12 July 2019)
Research

Tumor mutation burden and circulating tumor DNA in combined CTLA-4 and PD-1 antibody therapy in metastatic melanoma – results of a prospective biomarker study

Andrea Forschner, Florian Battke, Dirk Hadaschik, Martin Schulze, Stephanie Weißgraeber, Chung-Ting Han, Maria Kopp, Maximilian Frick, Bernhard Klumpp, Nicola Tietze, Teresa Amaral, Peter Martus, Tobias Sinnberg, Thomas Eigentler, Ulrike Keim, Claus Garbe, Dennis Döcker & Saskia Biskup
Journal for ImmunoTherapy of Cancer, 7:180 (12 July 2019)
Research

Response to combined ipilimumab and nivolumab after development of a nephrotic syndrome related to PD-1 monotherapy

Valerie Glutsch, Franziska Grän, Judith Weber, Anja Gesierich, Matthias Goebeler & Bastian Schilling
Journal for ImmunoTherapy of Cancer, 7:181 (12 July 2019)
Case Report

Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment

Daan P. Hurkmans, Jeroen G. H. P. Verhoeven, Kitty de Leur, Karin Boer, Arjen Joosse, Carla C. Baan, Jan H. von der Thüsen, Ron H. N. van Schaik, Ron H. J. Mathijssen, Astrid A. M. van der Veldt & Dennis A. Hesselink
Journal for ImmunoTherapy of Cancer, 7:182 (12 July 2019)
Case Report

Tumor mutational burden quantification from targeted gene panels: major advancements and challenges

Laura Fancello, Sara Gandini, Pier Giuseppe Pelicci & Luca Mazzarella
Journal for ImmunoTherapy of Cancer, 7:183 (15 July 2019)
Review

Molecular and metabolic pathways mediating curative treatment of a non-Hodgkin B cell lymphoma by Sindbis viral vectors and anti-4-1BB monoclonal antibody

Minjun Yu, Iris Scherwitzl, Silvana Opp, Aristotelis Tsirigos & Daniel Meruelo
Journal for ImmunoTherapy of Cancer, 7:185 (15 July 2019)
Research

Transgenerational transfer of gene-modified T cells

Cormac Cosgrove, Emilia R. Dellacecca, Joost H. van den Berg, John B. Haanen, Michael I. Nishimura, I. Caroline Le Poole & Hans E. N. Bergmans
Journal for ImmunoTherapy of Cancer, 7:186 (15 July 2019)
Hypothesis

miR-34a as hub of T cell regulation networks

Martin Hart, Barbara Walch-Rückheim, Lena Krammes, Tim Kehl, Stefanie Rheinheimer, Tanja Tänzer, Birgit Glombitza, Martina Sester, Hans-Peter Lenhof, Andreas Keller & Eckart Meese
Journal for ImmunoTherapy of Cancer, 7:187 (16 July 2019)
Research

Diverse immunotherapies can effectively treat syngeneic brainstem tumors in the absence of overt toxicity

Matthew R. Schuelke, Phonphimon Wongthida, Jill Thompson, Timothy Kottke, Christopher B. Driscoll, Amanda L. Huff, Kevin G. Shim, Matt Coffey, Jose Pulido, Laura Evgin & Richard G. Vile
Journal for ImmunoTherapy of Cancer, 7:188 (17 July 2019)
Research

Oncolytic Maraba virus armed with tumor antigen boosts vaccine priming and reveals diverse therapeutic response patterns when combined with checkpoint blockade in ovarian cancer

A. J. Robert McGray, Ruea-Yea Huang, Sebastiano Battaglia, Cheryl Eppolito, Anthony Miliotto, Kyle B. Stephenson, Amit A. Lugade, Gill Webster, Brian D. Lichty, Mukund Seshadri, Danuta Kozbor & Kunle Odunsi
Journal for ImmunoTherapy of Cancer, 7:189 (17 July 2019)
Research

A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients

Daan P. Hurkmans, Edwin A. Basak, Tanja van Dijk, Darlene Mercieca, Marco W. J. Schreurs, Annemarie J. M. Wijkhuijs, Sander Bins, Esther Oomen-de Hoop, Reno Debets, Markus Joerger, Arlette Odink, Astrid A. M. van der Veldt, Cor H. van der Leest, Joachim G. J. V. Aerts, Ron H. J. Mathijssen & Stijn L. W. Koolen
Journal for ImmunoTherapy of Cancer, 7:192 (19 July 2019)
Research

Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma

Yi Zheng, Tingting Wang, Xiaoxuan Tu, Yun Huang, Hangyu Zhang, Di Tan, Weiqin Jiang, Shunfeng Cai, Peng Zhao, Ruixue Song, Peilu Li, Nan Qin & Weijia Fang
Journal for ImmunoTherapy of Cancer, 7:193 (23 July 2019)
Short Report

Multiplex quantitative analysis of cancer-associated fibroblasts and immunotherapy outcome in metastatic melanoma

Pok Fai Wong, Wei Wei, Swati Gupta, James W. Smithy, Daniel Zelterman, Harriet M. Kluger & David L. Rimm
Journal for ImmunoTherapy of Cancer, 7:194 (23 July 2019)
Research

Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma

Nicholas D. Klemen, Melinda Wang, Paul L. Feingold, Kirsten Cooper, Sabrina N. Pavri, Dale Han, Frank C. Detterbeck, Daniel J. Boffa, Sajid A. Khan, Kelly Olino, James Clune, Stephan Ariyan, Ronald R. Salem, Sarah A. Weiss, Harriet M. Kluger, Mario Sznol & Charles Cha
Journal for ImmunoTherapy of Cancer, 7:196 (24 July 2019)
Research

A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1–3 inhibitor, cediranib, in recurrent women’s cancers with biomarker analyses

Alexandra S. Zimmer, Erin Nichols, Ashley Cimino-Mathews, Cody Peer, Liang Cao, Min-Jung Lee, Elise C. Kohn, Christina M. Annunziata, Stanley Lipkowitz, Jane B. Trepel, Rajni Sharma, Lekha Mikkilineni, Margaret Gatti-Mays, William D. Figg, Nicole D. Houston & Jung-Min Lee
Journal for ImmunoTherapy of Cancer, 7:197 (25 July 2019)
Short Report

Epigenetic alterations are associated with tumor mutation burden in non-small cell lung cancer

Liangliang Cai, Hua Bai, Jianchun Duan, Zhijie Wang, Shugeng Gao, Di Wang, Shuhang Wang, Jun Jiang, Jiefei Han, Yanhua Tian, Xue Zhang, Hao Ye, Minghui Li, Bingding Huang, Jie He & Jie Wang
Journal for ImmunoTherapy of Cancer, 7:198 (26 July 2019)
Research

Combination therapy targeting both innate and adaptive immunity improves survival in a pre-clinical model of ovarian cancer

Christina A. Hartl, Adrian Bertschi, Regina Bou Puerto, Carolin Andresen, Emily M. Cheney, Elizabeth A. Mittendorf, Jennifer L. Guerriero & Michael S. Goldberg
Journal for ImmunoTherapy of Cancer, 7:199 (30 July 2019)
Research

Perilesional edema in brain metastases: potential causes and implications for treatment with immune therapy

Thuy T. Tran, Amit Mahajan, Veronica L. Chiang, Sarah B. Goldberg, Don X. Nguyen, Lucia B. Jilaveanu & Harriet M. Kluger
Journal for ImmunoTherapy of Cancer, 7:200 (30 July 2019)
Short Report

Targeting Interleukin(IL)-30/IL-27p28 signaling in cancer stem-like cells and host environment synergistically inhibits prostate cancer growth and improves survival

Carlo Sorrentino, Zhinan Yin, Stefania Ciummo, Paola Lanuti, Li-Fan Lu, Marco Marchisio, Matteo Bellone & Emma Di Carlo
Journal for ImmunoTherapy of Cancer, 7:201 (31 July 2019)
Research

SITC Members Receive 60 Percent Submission Discount in 2019

*As a way to thank the SITC members who work tirelessly to advance the science and improve the lives of cancer patients, SITC will provide SITC members with a 60 percent discount on processing fees for all JITC articles accepted in 2019. To take advantage of this SITC member benefit, authors must contact JITC Managing Editor Andrea Kunz at JITCEditor@sitcancer.org or 1-414-271-2456 prior to submission to obtain a discount code and instructions.