JITC Digest March 2019

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Inside this Issue:

Letter from the Editor

Dear JITC Readers,pedro-romero_1__1_.jpg

In the March edition of the JITC Digest, there are five important articles of which I would like to draw attention. First, the article “HDAC6 selective inhibition of melanoma patient T-cells augments anti-tumor characteristics,” by Andressa S. Laino et al. details the development of two HDAC6-selective inhibitors, ACY-1215 and ACY-241 as modulators of human T cell properties. Through ex vivo studies and at concentrations achievable in human patients, the reported HDAC6 inhibitors did considerably enhance melanoma patient T cell functions suggesting potential therapeutic efficacy.

Next, the research article, “Persistent mutant oncogene specific T cells in two patients benefitting from anti-PD-1,” by Kellie N. Smith et al. reports two cases of patients with biomarker-negative tumors (low mutational burden, negative for PD-L1, MMR proficient), each of which maintained a T cell response to a hotspot oncogenic mutation years after treatment initiation and both of whom derived durable clinical benefit from PD-1 blockade. Such results demonstrate that driver mutations may elicit efficient and durable anti-tumor immune responses and augment clinical response to immunotherapy.

Furthermore, the article, “Cancer-cell-secreted CXCL11 promoted CD8+ T cells infiltration through docetaxel-induced-release of HMGB1 in NSCLC,” by Qun Gao et al. presents novel data demonstrating the ability of docetaxel to upregulate CXCL11 in the tumor microenvironment through the release of HMGB1, subsequently driving the recruitment of CD8+ T cells and eliciting an improved immune response. This data supports the further development of clinical studies to measure anti-tumor immune response after docetaxel treatment in cancer patients.

“The IL-1/IL-1 receptor axis and tumor cell released inflammasome adaptor ASC are key regulators of TSLP secretion by cancer associated fibroblasts in pancreatic cancer,” by Emanuela Brunetto et al. identified tumor-derived IL-1α and IL-1β as key cytokines in driving thymic stromal lymphopoietin (TLSP) secretion by cancer associated fibroblasts and tumor-released ASC. Results also demonstrate that treatment with an IL-1R antagonist significantly reduces TSLP expression in in vivo tumor models, providing support to the further assessment of therapies which aim to interfere with such pathways.

Finally, Cynthia Perez et al.’s article, “NKG2D signaling certifies effector CD8 T cells for memory formation,” shows that signaling through NKG2D in primary effector CD8 T cells is required for their differentiation into functional memory cells. As a better understanding of how long-term memory cells are formed from the initial effector pool of CD8 T cells remains an essential objective in immunology, this process of “memory certification” provides important clues to the development of improved vaccines and adoptive cellular therapies.

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


JITC Editor Picks

HDAC6 selective inhibition of melanoma patient T-cells augments anti-tumor characteristics

Andressa S. Laino, B. C. Betts, A. Veerapathran, I. Dolgalev, A. Sarnaik, S. N. Quayle, S. S. Jones, J. S. Weber and David M. Woods
Journal for ImmunoTherapy of Cancer, 7:30 (15 February 2019)
Research Article

Summary:

With a proven ability to promote direct tumor cytotoxicity and alter tumor immunogenicity, several pan-HDAC inhibitors (HDACi) are FDA-approved for the treatment of hematologic malignancies. However, the direct effects of HDACi on T cells remain ill defined and have shown to be dependent on the timing, potency, dose and specificity of the inhibitor used. In the present study, Laino et al. systemically analyzed the effects of selective HDAC6 inhibition on the immune properties of T cells derived from melanoma patients’ PBMCs and tumor. Results demonstrate that two HDAC6-selective inhibitors effectively augmented melanoma patient T cell phenotypes and functional competence at concentrations achievable in human patients, supporting future pre-clinical and clinical studies.

Persistent mutant oncogene specific T cells in two patients benefitting from anti-PD-1

Kellie N. Smith, Nicolas J. Llosa, Tricia R. Cottrell, Nicholas Siegel, Hongni Fan, Prerna Suri, Hok Yee Chan, Haidan Guo, Teniola Oke, Anas H. Awan, Franco Verde, Ludmila Danilova, Valsamo Anagnostou, Ada J. Tam, Brandon S. Luber, Bjarne R. Bartlett, Laveet K. Aulakh, John-William Sidhom, Qingfeng Zhu, Cynthia L. Sears, Leslie Cope, William H. Sharfman, Elizabeth D. Thompson, Joanne Riemer, Kristen A. Marrone, Jarushka Naidoo, Victor E. Velculescu, Patrick M. Forde, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Jennifer N. Durham, Hao Wang, Dung T. Le, Sune Justesen, Janis M. Taube, Luis A. Diaz Jr, Julie R. Brahmer, Drew M. Pardoll, Robert A. Anders and Franck Housseau
Journal for ImmunoTherapy of Cancer, 7:30 (15 February 2019)
Research Article

Summary:

Although tumors with high PD-L1 expression, high TMB, or mismatch repair deficiency (MMRd) are more likely to respond to checkpoint blockade, some patients without MMR deficient or high TMB cancers derive clinical benefit from PD-1 pathway inhibitors. To better understand such outliers and provide insight into improving immunotherapy outcomes, Smith et al. assessed two cases of patients with biomarker-negative tumors who derived durable clinical benefit from PD-1 blockade monotherapy: a NSCLC patient whose tumor had 30 mutations and was negative for PD-L1 and a MMR proficient CRC patient. Interestingly, each patient maintained a T cell response to a hotspot oncogenic mutation for years post-treatment initiation: BRAF N581I (NSCLC pt) and AKT1 E17K (CRC pt), providing foundational evidence that immunogenic oncogene-derived neoantigens may potentiate endogenous T cell responses.

Cancer-cell-secreted CXCL11 promoted CD8+ T cells infiltration through docetaxel-induced-release of HMGB1 in NSCLC

Qun Gao, Shumin Wang, Xinfeng Chen, Shaoyan Cheng, Zhen Zhang, Feng Li, Lan Huang, Yang Yang, Bin Zhou, Dongli Yue, Dan Wang, Ling Cao, Nomathamsanqa Resegofetse Maimela, Bin Zhang, Jane Yu, Liping Wang and Yi Zhang
Journal for ImmunoTherapy of Cancer, 7:30 (15 February 2019)
Research Article

Summary:

Promising clinical evidence indicates that combining chemotherapy with immunotherapy can either stimulate or augment an immune response. While the mechanism remains unknown, previous studies have demonstrated that the addition of docetaxel has the ability to decrease regulatory T cell subsets and myeloid-derived suppressor cells in NSCLC patients and enhance IFN-γ production by CD8+ T cells in murine models. Thus, as high numbers of infiltrating cytotoxic T lymphocytes and low numbers of tumor-associated immune suppressor cells tend to correlate with favorable prognosis, Gao et al. present a novel mechanism by which docetaxel promotes immune function through modulation of HMGB1 and CXCL11 expression and subsequent CD8+ T cell infiltration to the tumor microenvironment, ultimately improving anti-tumor efficacy in patients with NSCLC.

The IL-1/IL-1 receptor axis and tumor cell released inflammasome adaptor ASC are key regulators of TSLP secretion by cancer associated fibroblasts in pancreatic cancer

Emanuela Brunetto, Lucia De Monte, Gianpaolo Balzano, Barbara Camisa, Vincenzo Laino, Michela Riba, Silvia Heltai, Marco Bianchi, Claudio Bordignon, Massimo Falconi, Attilio Bondanza, Claudio Doglioni and Maria Pia Protti
Journal for ImmunoTherapy of Cancer, 7:30 (15 February 2019)
Research Article

Summary:

Previously reported data by the Brunetto group showed that the ratio of Th2 over Th1 lymphocytes in the tumor stroma is an independent predictive factor of survival after surgery in pancreatic ductal adenocarcinoma (PDAC) patients, with greater Th2 levels correlating with reduced survival. While the thymic stromal lymphopoietin (TSLP) is known to be a chief cytokine for development of Th2 immunity, the driving mechanism behind TSLP secretion in PDAC remains elusive. Brunetto et al. present a novel cell signaling mechanism by which IL-1α and IL-1β secreted from tumor cells play a key role in TSLP production, where IL-1β secretion in particular is driven by the inflammasome adaptor ASC, whose expression in pancreatic cancer surgical samples correlates inversely with patient survival.

NKG2D signaling certifies effector CD8 T cells for memory formation

Cynthia Perez, Kushal Prajapati, Brianna Burke, Lourdes Plaza-Rojas, Nancy J. Zeleznik-Le and Jose A. Guevara-Patino
Journal for ImmunoTherapy of Cancer, 7:30 (15 February 2019)
Research Article

Summary:

NKG2D signaling has been shown to induce transcription of memory-associated genes, have a functional relationship with IL-15 signaling, be linked with memory formation and to also play no major role at all in memory CD8 T cell differentiation. Thus, the importance of NKG2D signaling in the formation of memory cells remains unclear. Perez et al. showed that NKG2D signaling plays a fundamental role in CD8 T cell memory formation, specifically during the effector differentiation phase of a primary CD8 T cell response. Ultimately, this process of “certification” for T cell memory formation could contribute to guiding the development of better vaccines and adoptive cell therapies.

TNF-α enhances Th9 cell differentiation and antitumor immunity via TNFR2-dependent pathways

Yuxue Jiang, Jintong Chen, Enguang Bi, Yinghua Zhao, Tianxue Qin, Yiming Wang, Alison Wang, Sujun Gao, Qing Yi and Siqing Wang
Journal for ImmunoTherapy of Cancer, 7:28 (4 February 2019)
Research Article

Immunotherapy of triple-negative breast cancer with cathepsin D-targeting antibodies

Yahya Ashraf, Hanane Mansouri, Valérie Laurent-Matha, Lindsay B. Alcaraz, Pascal Roger, Séverine Guiu, Danielle Derocq, Gautier Robin, Henri-Alexandre Michaud, Helène Delpech, Marta Jarlier, Martine Pugnière, Bruno Robert, Anthony Puel, Lucie Martin, Flavie Landomiel, Thomas Bourquard, Oussama Achour, Ingrid Fruitier-Arnaudin, Alexandre Pichard, Emmanuel Deshayes, Andrei Turtoi, Anne Poupon, Joëlle Simony-Lafontaine, Florence Boissière-Michot, Nelly Pirot, Florence Bernex, William Jacot, Stanislas du Manoir, Charles Theillet, Jean-Pierre Pouget, Isabelle Navarro-Teulon, Nathalie Bonnefoy, André Pèlegrin, Thierry Chardès, Pierre Martineau and Emmanuelle Liaudet-Coopman
Journal for ImmunoTherapy of Cancer, 7:29 (4 February 2019)
Research Article

Avelumab (anti–PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial

Hyun Cheol Chung, Hendrik-Tobias Arkenau, Jeeyun Lee, Sun Young Rha, Do-Youn Oh, Lucjan Wyrwicz, Yoon-Koo Kang, Keun-Wook Lee, Jeffrey R. Infante, Sung Sook Lee, Margaret Kemeny, Ulrich Keilholz, Bohuslav Melichar, Alain Mita, Ruth Plummer, Denis Smith, Arnold B. Gelb, Huiling Xiong, Janet Hong, Vikram Chand and Howard Safran
Journal for ImmunoTherapy of Cancer, 7:30 (4 February 2019)
Research Article

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced pancreatic injury

Hamzah Abu-Sbeih, Tenglong Tang, Yang Lu, Selvi Thirumurthi, Mehmet Altan, Amir A. Jazaeri, Ramona Dadu, Emmanuel Coronel and Yinghong Wang
Journal for ImmunoTherapy of Cancer, 7:31 (6 February 2019)
Research Article

Suppression of Myeloid Cell Arginase Activity leads to Therapeutic Response in a NSCLC Mouse Model by Activating Anti-Tumor Immunity

Juan J. Miret, Paul Kirschmeier, Shohei Koyama, Mingrui Zhu, Yvonne Y. Li, Yujiro Naito, Min Wu, Venkat S. Malladi, Wei Huang, William Walker, Sangeetha Palakurthi, Glenn Dranoff, Peter S. Hammerman, Chad V. Pecot, Kwok-Kin Wong and Esra A. Akbay
Journal for ImmunoTherapy of Cancer, 7:32 (6 February 2019)
Research Article

Prognostic value of CD8 + PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer

Joe Yeong, Jeffrey Chun Tatt Lim, Bernett Lee, Huihua Li, Clara Chong Hui Ong, Aye Aye Thike, Wei Hseun Yeap, Yi Yang, Ansel Yi Herh Lim, Timothy Kwang Yong Tay, Jin Liu, Siew-Cheng Wong, Jinmiao Chen, Elaine Hsuen Lim, Jabed Iqbal, Rebecca Dent, Evan W. Newell and Puay Hoon Tan
Journal for ImmunoTherapy of Cancer, 7:34 (6 February 2019)
Research Article

Different role of circulating myeloid-derived suppressor cells in patients with multiple myeloma undergoing autologous stem cell transplantation

Sung-Eun Lee, Ji-Young Lim, Tae Woo Kim, Da-Bin Ryu, Sung Soo Park, Young-Woo Jeon, Jae-Ho Yoon, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Seok-Goo Cho, Dong-Wook Kim, Jong Wook Lee and Chang-Ki Min
Journal for ImmunoTherapy of Cancer, 7:35 (7 February 2019)
Research Article

Allogenic Vγ9Vδ2 T cell as new potential immunotherapy drug for solid tumor: a case study for cholangiocarcinoma

Mohammed Alnaggar, Yan Xu, Jingxia Li, Junyi He, Jibing Chen, Man Li, Qingling Wu, Li Lin, Yingqing Liang, Xiaohua Wang, Jiawei Li, Yi Hu, Yan Chen, Kecheng Xu, Yangzhe Wu and Zhinan Yin
Journal for ImmunoTherapy of Cancer, 7:36 (8 February 2019)
Case Report

Characterization of immune responses to anti-PD-1 mono and combination immunotherapy in hematopoietic humanized mice implanted with tumor xenografts

A. Capasso, J. Lang, T. M. Pitts, K. R. Jordan, C. H. Lieu, S. L. Davis, J. R. Diamond, S. Kopetz, J. Barbee, J. Peterson, B. M. Freed, B. W. Yacob, S. M. Bagby, W. A. Messersmith, J. E. Slansky, R. Pelanda and S. G. Eckhardt
Journal for ImmunoTherapy of Cancer, 7:37 (8 February 2019)
Research Article

Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer

Alexandros Papachristofilou, Madeleine M. Hipp, Ute Klinkhardt, Martin Früh, Martin Sebastian, Christian Weiss, Miklos Pless, Richard Cathomas, Wolfgang Hilbe, Georg Pall, Thomas Wehler, Jürgen Alt, Helge Bischoff, Michael Geißler, Frank Griesinger, Karl-Josef Kallen, Mariola Fotin-Mleczek, Andreas Schröder, Birgit Scheel, Anke Muth, Tobias Seibel, Claudia Stosnach, Fatma Doener, Henoch S. Hong, Sven D. Koch, Ulrike Gnad-Vogt and Alfred Zippelius
Journal for ImmunoTherapy of Cancer, 7:38 (8 February 2019)
Research Article

Are tumor size changes predictive of survival for checkpoint blockade based immunotherapy in metastatic melanoma?

Meihua Wang, Cong Chen, Thomas Jemielita, James Anderson, Xiaoyun (Nicole) Li, Chen Hu, S. Peter Kang, Nageatte Ibrahim and Scot Ebbinghaus
Journal for ImmunoTherapy of Cancer, 7:39 (8 February 2019)
Research Article

Antitumor response to microscopic melanoma in the gastric mucosa mimicking ipilimumab-induced gastritis

Elisa Bello, Justine V. Cohen, Mari Mino-Kenudson and Michael Dougan
Journal for ImmunoTherapy of Cancer, 7:41 (11 February 2019)
Research Article

Efficacy of PD-1 blockade in cervical cancer is related to a CD8+FoxP3+CD25+ T-cell subset with operational effector functions despite high immune checkpoint levels

A. M. Heeren, J. Rotman, A. G. M. Stam, N. Pocorni, A. A. Gassama, S. Samuels, M. C. G. Bleeker, C. H. Mom, H. J. M. A. A. Zijlmans, G. G. Kenter, E. S. Jordanova and T. D. de Gruijl
Journal for ImmunoTherapy of Cancer, 7:43 (12 February 2019)
Research Article

The motility regulator flhDC drives intracellular accumulation and tumor colonization of Salmonella

Vishnu Raman, Nele Van Dessel, Owen M. O’Connor and Neil S. Forbes
Journal for ImmunoTherapy of Cancer, 7:44 (12 February 2019)
Research Article

Acute liver injury in the context of immune checkpoint inhibitor-related colitis treated with infliximab

Hao Chi Zhang, Wenyi Luo and Yinghong Wang
Journal for ImmunoTherapy of Cancer, 7:47 (18 February 2019)
Case Report

Therapy with high-dose Interleukin-2 (HD IL-2) in metastatic melanoma and renal cell carcinoma following PD1 or PDL1 inhibition

Elizabeth I. Buchbinder, Janice P. Dutcher, Gregory A. Daniels, Brendan D. Curti, Sapna P. Patel, Shernan G. Holtan, Gerald P. Miletello, Mayer N. Fishman, Rene Gonzalez, Joseph I. Clark, John M. Richart, Christopher D. Lao, Scott S. Tykodi, Ann W. Silk and David F. McDermott
Journal for ImmunoTherapy of Cancer, 7:49 (18 February 2019)
Research Article

Antibodies as biomarker candidates for response and survival to checkpoint inhibitors in melanoma patients

Mirjam Fässler, Stefan Diem, Joanna Mangana, Omar Hasan Ali, Fiamma Berner, David Bomze, Sandra Ring, Rebekka Niederer, Cristina del Carmen Gil Cruz, Christian Ivan Pérez Shibayama, Michal Krolik, Marco Siano, Markus Joerger, Mike Recher, Lorenz Risch, Sabine Güsewell, Martin Risch, Daniel E. Speiser, Burkhard Ludewig, Mitchell P. Levesque, Reinhard Dummer and Lukas Flatz
Journal for ImmunoTherapy of Cancer, 7:50 (20 February 2019)
Research Article

A good response of refractory mantel cell lymphoma to haploidentical CAR T cell therapy after failure of autologous CAR T cell therapy

Tongjuan Li, Yuanyuan Zhang, Dan Peng, Xia Mao, Xiaoxi Zhou and Jianfeng Zhou
Journal for ImmunoTherapy of Cancer, 7:51 (21 February 2019)
Case Report

Inflammation-induced hypoparathyroidism triggered by combination immune checkpoint blockade for melanoma

Beckey Trinh, Guacimara Ortega Sanchez, Petra Herzig and Heinz Läubli
Journal for ImmunoTherapy of Cancer, 7:52 (21 February 2019)
Case Report

Influenza vaccination and myocarditis among patients receiving immune checkpoint inhibitors

Magid Awadalla, Doll Lauren Alexandra Golden, Syed S. Mahmood, Raza M. Alvi, Nathaniel D. Mercaldo, Malek Z. O. Hassan, Dahlia Banerji, Adam Rokicki, Connor Mulligan, Sean P. T. Murphy, Maeve Jones-O’Connor, Justine V. Cohen, Lucie M. Heinzerling, Merna Armanious, Ryan J. Sullivan, Rongras Damrongwatanasuk, Carol L. Chen, Dipti Gupta, Michael C. Kirchberger, Javid J. Moslehi, Sachin P. Shah, Sarju Ganatra, Paaladinesh Thavendiranathan, Muhammad A. Rizvi, Gagan Sahni, Alexander R. Lyon, Carlo G. Tocchetti, Valentina Mercurio, Franck Thuny, Stephane Ederhy, Michael Mahmoudi, Donald P. Lawrence, John D. Groarke, Anju Nohria, Michael G. Fradley, Kerry L. Reynolds and Tomas G. Neilan
Journal for ImmunoTherapy of Cancer, 7:53 (22 February 2019)
Research Article

Increased intratumoral mast cells foster immune suppression and gastric cancer progression through TNF-α-PD-L1 pathway

Yipin Lv, Yongliang Zhao, Xianhua Wang, Na Chen, Fangyuan Mao, Yongsheng Teng, Tingting Wang, Liusheng Peng, Jinyu Zhang, Ping Cheng, Yugang Liu, Hui Kong, Weisan Chen, Chuanjie Hao, Bin Han, Qiang Ma, Quanming Zou, Jun Chen and Yuan Zhuang
Journal for ImmunoTherapy of Cancer, 7:54 (15 February 2019)
Research Article

Combination treatment with hypofractionated radiotherapy plus IL-2/anti-IL-2 complexes and its theranostic evaluation

Hua Jing, Michael Hettich, Simone Gaedicke, Elke Firat, Mark Bartholomä and Gabriele Niedermann
Journal for ImmunoTherapy of Cancer, 7:55 (26 February 2019)
Research Article

A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable

Alessio Cortellini, Melissa Bersanelli, Sebastiano Buti, Katia Cannita, Daniele Santini, Fabiana Perrone, Raffaele Giusti, Marcello Tiseo, Maria Michiara, Pietro Di Marino, Nicola Tinari, Michele De Tursi, Federica Zoratto, Enzo Veltri, Riccardo Marconcini, Francesco Malorgio, Marco Russano, Cecilia Anesi, Tea Zeppola, Marco Filetti, Paolo Marchetti, Andrea Botticelli, Gian Carlo Antonini Cappellini, Federica De Galitiis, Maria Giuseppa Vitale, Francesca Rastelli, Federica Pergolesi, Rossana Berardi, Silvia Rinaldi, Marianna Tudini, Rosa Rita Silva, Annagrazia Pireddu, Francesco Atzori, Rita Chiari, Biagio Ricciuti, Andrea De Giglio, Daniela Iacono, Alain Gelibter, Mario Alberto Occhipinti, Alessandro Parisi, Giampiero Porzio, Maria Concetta Fargnoli, Paolo Antonio Ascierto, Corrado Ficorella and Clara Natoli
Journal for ImmunoTherapy of Cancer, 7:57 (27 February 2019)
Research Article

The immune suppressive microenvironment of human gliomas depends on the accumulation of bone marrow-derived macrophages in the center of the lesion

Laura Pinton, Elena Masetto, Marina Vettore, Samantha Solito, Sara Magri, Marta D’Andolfi, Paola Del Bianco, Giovanna Lollo, Jean-Pierre Benoit, Hideho Okada, Aaron Diaz, Alessandro Della Puppa and Susanna Mandruzzato
Journal for ImmunoTherapy of Cancer, 7:58 (27 February 2019)
Research Article

Intralymphatic histiocytosis in a patient with lung adenocarcinoma treated with pembrolizumab: a case report

Teppei Sugano, Masahiro Seike, Yoko Funasaka, Mai Yoshida, Ryoko Takayama, Ken Okamura, Asuka Nakanishi, Toru Tanaka, Susumu Takeuchi, Rintaro Noro, Yuji Minegishi, Kaoru Kubota, Hidehisa Saeki and Akihiko Gemma
Journal for ImmunoTherapy of Cancer, 7:59 (27 February 2019)
Case Report

A novel TLR4 binding protein, 40S ribosomal protein S3, has potential utility as an adjuvant in a dendritic cell-based vaccine

Hyun Jin Park, Gun-Young Jang, Young Seob Kim, Jung Hwa Park, Sung Eun Lee, Manh-Cuong Vo, Je-Jung Lee, Hee Dong Han, In Duk Jung, Tae Heung Kang and Yeong-Min Park
Journal for ImmunoTherapy of Cancer, 7:60 (28 February 2019)
Research Article

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.