JITC Digest April 2020

jitc-logo.gif

Inside this Issue:

Letter from the Editor

Dear JITC Readers,pedro-romero_1__1_.jpg

Even as the COVID-19 pandemic continues to challenge almost all aspects of daily life, JITC remains unwavering in our commitment to publishing the very best that the immunotherapy field has to offer. Although SARS-CoV-2 is radically changing how we as a community care for our patients and conduct our research, you can count on JITC as a constant source for new findings and important insights from across the spectrum of immuno-oncology. 

This month, the JITC digest offers several papers that develop intriguing strategies to boost antitumor immune responses. Jahangir Ahmed and colleagues engineered a replication-competent oncolytic vaccinia virus that delivers IL-12 to the tumor microenvironment, prolonging survival and controlling lung metastases when administered as an adjuvant to surgical excision in mouse models. Modulation of the tumor microenvironment also synergized with checkpoint blockade in a paper by Lucas A. Horn et al., where combined inhibition of TGF-beta and IL-8 signaling attenuated epithelial to mesenchymal transition in models of both breast and lung cancer. Additionally, Yong Li and colleagues revealed a key role in signaling through the innate immune danger-recognition sensor RIG-I in the development of interferon resistance in melanoma tumor-regenerating cells, identifying STAT3 as a potential therapeutic target. 

Also this month, in a paper that will surely prove reassuring, Nicholas Bevins and colleagues rigorously analyzed the impact of different methods of calculating tumor mutational burden and found good correlation between approaches. 

Finally, be sure not to miss an outstanding review by Lorenzo Galluzzi et al. that delivers a thorough overview of immunologic cell death with detailed discussions of the biological mechanisms leading to the establishment of immunologic memory, the available assays to measure key phenomena, and the hurdles to overcome for translation into clinical benefit. 
 
Best regards,

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


JITC Editor Picks

A new oncolytic Vaccinia virus auguments antitumor immune responses to prevent tumor recurrence and metastasis after surgery 

Jahangir Ahmed, Louisa S Chard, Ming Yuan, Jiwei Wang, Anwen Howells, Yuenan Li, Haoze Li, Zhongxian Zhang, Shuangshuang Lu, Dongling Gao, Pengju Wang, Yongchao Chu, Chadwan Al Yaghchi, Joel Schwartz, Ghassan Alusi, Nicholas Lemoine, Yaohe Wang
Journal for ImmunoTherapy of Cancer 2020;8:e000415 (26 March 2020)
Research

Summary:

Oncolytic viruses may be a promising option to reduce recurrence and metastasis of solid tumors after surgery due to microscopic deposits of minimal residual disease (MRD) beyond the clearance margins. Reasoning that deletion of the N1L gene (which produces a product that potently suppresses proinflammatory NF-kappa-B signaling) from vaccinia virus may serve to locally enhance the innate antiviral immune responses, Jahangir Ahmed et al. engineered VVdeltaTKdeltaN1L—a replication competent oncolytic virus that controlled a variety of aggressive tumors including lung, pancreatic and head and neck cancers in mouse models. Intratumoral injection of the virus increased the numbers of infiltrating CD8+ and CD4+ T cells, and splenocytes isolated 7 and 14 days after treatment displayed enhanced effector CD8+ T cell populations. Treatment was also associated with elevated levels of proinflammatory cytokines, including IL-1beta and interferon gamma. The addition of IL-12 to the engineered virus further enhanced its antitumor properties, leading to a 90% cure rate, compared to 60% with the parent strain. When given as adjuvant prior to surgical excision of flank tumors, the IL-12-augmented oncolytic virus controlled lung metastases and extended long-term survival. The IL-12-producing oncolytic virus could be a promising agent for use as an adjuvant to surgical treatment of solid tumors.

Comparison of commonly used solid tumor targeted gene sequencing panels for estimating tumor mutation burden shows analytical and prognostic concordance within the cancer genome atlas cohort

Nicholas Bevins, Shulei Sun, Zied Gaieb, John A Thorson and Sarah S Murray

Journal for ImmunoTherapy of Cancer 2020;8:e000613  (26 March 2020)
Research

Summary:

Tumor mutational burden (TMB) values can predict responses to immune checkpoint inhibitor therapy, but calculation methods including the content of gene panels sequenced (the denominator of TMB) and the inclusion of synonymous variants (the numerator of TMB) are not standardized between institutions. To understand the impact of altering these parameters, Nicholas Bevins et al. used publicly available data for more than 9000 tumors from The Cancer Genome Atlas (TCGA) to perform in silico simulations of TMB calculations by six commonly used molecular profiling products. The correlation between panel-based and whole-exome sequencing-based method was linear and the correlations between individual panel-based TMB calculations showed slopes of 0.9-1.1, indicating that the absolute value is comparable between panels. For TMB calculations derived from whole-exome sequencing, inclusion of synonymous variants led to differences of roughly 5-10 variants/Mb specifically in the approximate clinical decision range of TMB <20. By contrast, inclusion of synonymous variants in panel-based TMB calculations did not cause any differences in values for panels of similar size. Although most of the datasets in TCGA were deposited before the widespread use and FDA approval of checkpoint inhibitors, analysis of pan-tumor data showed an inverse correlation between TMB and overall survival, though this relationship varied for individual subgroups of cancers. The analysis provides reassuring confirmation that TMB calculations between the gene panels examined are analytically and prognostically equivalent.

Simultaneous inhibition of CXCR1/2, TGF-beta, and PD-L1 remodels the tumor and its microenvironment to drive antitumor immunity

Lucas A Horn, Jeffrey Riskin, Heidi A Hempel, Kristen Fousek, Hanne Lind, Duane H Hamilton, Kristen K McCampbell, Dean Y Maeda, John A Zebala, Zhen Su, Jeffrey Schlom and Claudia Palena
Journal for ImmunoTherapy of Cancer 2020;8:e000326 (17 March 2020)
Research

Summary:

Tumor cell plasticity induced in the context of an epithelial-mesenchymal transition (EMT) has been implicated in primary resistance to checkpoint blockade. Lucas A. Horn and colleagues demonstrated synergistic tumor control in mouse models of lung and breast cancer through a combination of checkpoint inhibition and EMT modulation. Treatment with a combination of bintrafusp alfa (a bifunctional anti-PD-L1/TGF-B receptor trap) and SX-682 (a clinical stage, small molecule inhibitor that allosterically binds to the intracellular domain of CXCR1/2 and irreversibly inhibits downstream IL-8 signaling) reduced plasticity as measured by expression of mesenchymal fibronectin and vimentin. Single-agent SX-682 or bintrafusp alfa each similarly downregulated expression of matrix metalloproteinases as well as interleukin 1 alpha, and combination treatment caused pronounced modulation of numerous genes involved in remodeling the tumor microenvironment including interferon gamma, CD40lgIcosl and IL2rg. Serum cytokines from combination-treated mice were marked by high levels of Th1 polarizing cytokines IL-12 and tumor necrosis factor alpha and Th2 polarizing cytokines IL-4 and IL-5. The results highlight the potential benefit of combined blockade of IL-8 and TGF-beta signaling to enhance responses to checkpoint blockade by modulating tumor plasticity.

Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

Lorenzo Galluzzi, Ilio Vitale, Sarah Warren, Sandy Adjemian, Patrizia Agostinis, Aitziber Buqué Martinez, Timothy A Chan, George Coukos, Sandra Demaria, Eric Deutsch, Dobrin Draganov, Richard L Edelson, Silvia C Formenti, Jitka Fucikova, Lucia Gabriele, Udo S Gaipl, Sofia R Gameiro, Abhishek D Garg, Encouse Golden, Jian Han, Kevin J Harrington, Akseli Hemminki, James W Hodge, Dewan Md Sakib Hossain, Tim Illidge, Michael Karin, Howard L Kaufman, Oliver Kepp, Guido Kroemer, Juan Jose Lasarte, Sherene Loi, Michael T Lotze, Gwenola Manic, Taha Merghoub, Alan A Melcher, Karen L Mossman, Felipe Prosper, Øystein Rekdal, Maria Rescigno, Chiara Riganti, Antonella Sistigu, Mark J Smyth, Radek Spisek, John Stagg, Bryan E Strauss, Daolin Tang, Kazuki Tatsuno, Stefaan W van Gool, Peter Vandenabeele, Takahiro Yamazaki, Dmitriy Zamarin, Laurence Zitvogel, Alessandra Cesano and Francesco M Marincola
Journal for ImmunoTherapy of Cancer 2020;8:e000337 (9 March 2020)
Review

Summary:

Many therapies commonly used in the management of cancer patients induce a functionally unique form of stress-driven regulated cell death that culminates with the activation of cytotoxic T lymphocyte-driven adaptive immunity coupled with the establishment of long-term immunological memory. In a comprehensive review, Lorenzo Galluzzi and colleagues provide an operational definition of this immunogenic cell death, explain the underlying biological mechanisms and describe available assays along with guidelines for interpretation. The Nomenclature Committee on Cell Death recently defined immunogenic cell death as 'a form of regulated cell death that is sufficient to activate an adaptive immune response in immunocompetent syngeneic hosts.' Inducers of immunogenic cell death generally operate by driving emission of danger-associated molecular patterns (DAMPs) such as endogenous RNA, cytosolic DNA, or surface expression of endoplasmic reticulum chaperones. Conversely, the tumor microenvironment may antagonize responses to immunogenic cell death through the presence of regulatory T cells, M2-polarized tumor-associated macrophages and myeloid-derived suppressor cells. In the oncology setting, commonly used methods to assess immunogenic cell death in vitro typically measure cytokine and/or DAMP release or responses of antigen-presenting cells after exposure to dying cells. In vivo assays frequently rely on vaccination or evaluation of an abscopal response. Although interpretation of currently used assays can be challenging, especially given key differences between murine and human immunology, harnessing immunogenic cell death could potentially boost the clinical efficacy of many anti-cancer agents.

Downregulation of RIG-I mediated by ITGB3/c-SRC/STAT3 signaling confers resistance to interferon-alpha-induced apoptosis in tumor-repopulating cells of melanoma

Yong Li, Yingqiu Song, Pindong Li, Mingxing Li, Haizhou Wang, Tao Xu, Xiongjie Yu, Yuandong Yu, YunYan Tai, Ping Chen, Xiaojun Cai, Xianhe Wang, Longchao Xiang, Rui Deng, Xiufang Zhang, Liping Gao, Xuanbin Wang, Jing Liuand and Fengjun Cao
Journal for ImmunoTherapy of Cancer 2020;8:e000111 (8 March 2020)
Research

Summary:

Interferon alpha (IFN-a) has been widely and effectively used for the treatment of a variety of cancers, but resistance frequently develops. To study the role of tumor heterogeneity in interferon resistance, Yong Li et al. made use of a three-dimensional fibrin culture system to select and characterize a functionally defined subset of tumor-regenerating cells (TRCs) from previously-treated melanomas. Compared to flask-cultured cells of the same origin, TRCs underwent less apoptosis in response to IFN-a and displayed less activation of STAT1 as well as decreased expression of the apoptosis-related genes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), promyelocytic leukemia (PML) and 2'5'A oligoadenylate synthetase 1 (OAS1). Data from the cancer genome atlas revealed a correlation between high RIG-I expression and improved survival in melanoma patients and overexpression of RIG-I in TRCs restored interferon sensitivity, rescued TRAIL, PML and OAS1 expression in response to treatment and enhanced apoptotic cell death. STAT3 was highly phosphorylated in TRCs, which corresponded with decreased RIG-expression. No differences in IL-6 expression were observed between bulk-cultured cells and TRCs, however, inhibitors of cSRC and integrin beta 3 (ITGB3) both synergized with interferon. In mouse models, combination treatment with IFN-a and ITGB3 inhibitor increased apoptosis rates in ITGB3-high tumor cells. The study provides rationale for combining STAT3 inhibitors with IFN-a to enhance the efficacy of melanoma treatment.

Quality of life in long-term survivors of advanced melanoma treated with checkpoint inhibitors

Maha Mamoor, Michael A Postow, Jessica A Lavery, Shrujal S Baxi, Niloufer Khan, Jun J Mao, Lauren J Rogak, Robert Sidlow, Bridgette Thom, Jedd A Wolchok and Deborah Korenstein
Journal for ImmunoTherapy of Cancer 2020;8:e000260  (March 8 2020)
Research

Head-to-head comparison of in-house produced CD19 CAR-T cell in ALL and NHL patients

Orit Itzhaki, Elad Jacoby, Abraham Nissani, Michal Levi, Arnon Nagler, Adva Kubi, Karin Brezinger, Hadar Brayer, Li-at Zeltzer, Meir Rozenbaum, Helly Vernitsky, Gal Markel, Amos Toren, Abraham Avigdor, Jacob Schachter and Michal J Besser
Journal for ImmunoTherapy of Cancer
 
2020;8:e000148  (8 March 2020)
Research

Pre-existing antitherapeutic antibodies against the Fc region of the hu14.18K322A mAb are associated with outcome in patients with relapsed neuroblastoma

Jacob L Goldberg, Fariba Navid, Jacqueline A Hank, Amy K Erbe, Victor Santana, Jacek Gan, Fenna de Bie, Amal M Javaid, Anna Hoefges, Michael Merdler, Lakeesha Carmichael, KyungMann Kim, Michael W Bishop, Michael M Meager, Steven D Gillies, Janardan P Pandey and Paul M SondelJournal for ImmunoTherapy of Cancer 2020;8:e000590  (12 March 2020)
Short Report

Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab

Anna Minchom, Wei Yuan, Mateus Crespo, Bora Gurel, Ines Figueiredo, Andrew Wotherspoon, Susana Miranda, Ruth Riisnaes, Ana Ferreira, Claudia Bertan, Rita Pereira, Matt Clarke, Chloe Baker, Joo Ern Ang, Nicos Fotiadis, Nina Tunariu, Suzanne Carreira, Sanjay Popat, Mary O'Brien, Udai Banerji, Johann de Bono and Juanita Lopez
Journal for ImmunoTherapy of Cancer 2020;8:e000713  (12 March 2020)
Case Report

A case of dual-mechanism immune-related anaemia in a patient with metastatic melanoma treated with nivolumab and ipilimumab

Daniel J Olson, Padma Rajagopal, Melissa Y Tjota, Girish Venkataraman, Jason J Luke and Thomas F Gajewski
Journal for ImmunoTherapy of Cancer 2020;8:e000380  (12 March 2020)
Case Report

Peritumoral administration of IFN-beta upregulated mesenchymal stem cells inhibits tumor growth in an orthotopic, immunocompetent rat glioma model

Jiaji Mao, Minghui Cao, Fang Zhang, Jingzhong Zhang, Xiaohui Duan, Liejing Lu, Zehong Yang, Xiang Zhang, Wangshu Zhu, Qinyuan Zhang, Zhe Wang and Jun Shen
Journal for ImmunoTherapy of Cancer 2020;8:e000164  (12 March 2020)
Research

Pre-existing inflammatory immune microenvironment predicts the clinical response of vulvar high-grade squamous intraepithelial lesions to therapeutic HPV16 vaccination

Ziena Abdulrahman, Noel de Miranda, Edith M G van Esch, Peggy J de Vos van Steenwijk, Hans W Nijman, Marij J. P. Welters, Mariette I E van Poelgeest and Sjoerd H van der Burg
Journal for ImmunoTherapy of Cancer 2020;8:e000563  (12 March 2020)
Research

Potent STING activation stimulates immunogenic cell death to enhance antitumor immunity in neuroblastoma

Lihong Wang-Bishop, Mohamed Wehbe, Daniel Shae, Jamaal James, Benjamin C. Hacker, Kyle Garland, Plamen P. Chistov, Marjan Rafat, Justin M. Balko and John T. Wilson
Journal for ImmunoTherapy of Cancer 2020;8:e000282  (12 March 2020)
Research

Oncolytic vesicular stomatitis virus–based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8+ T-cell functionality

Seyedeh-Raheleh Niavarani, Christine Lawson, Marie Boudaud, Camille Simard and Lee-Hwa Tai
Journal for ImmunoTherapy of Cancer 
2020;8:e000465 (15 March 2020)
Research

A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti–PD-1 antibody, in patients with advanced solid tumors

Aung Naing, Justin F Gainor, Hans Gelderblom, Patrick M Forde, Marcus O Butler, Chia-Chi Lin, Sunil Sharma, Maria Ochoa de Olza, Andrea Varga, Matthew Taylor, Jan H M Schellens, Hongqian Wu, Haiying Sun, Antonio P Silva, Jason Faris, Jennifer Mataraza, Scott Cameron and Todd M Bauer
Journal for ImmunoTherapy of Cancer 2020;8:e000530  (15 March 2020)
Research

Compound kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib

Yang Yang, Mayu Sun, Wenbo Yao, Feng Wang, Xiaoguang Li, Wei Wang, Jingquan Li, Zhihu Gao, Lin Qiu, Rongli You, Chenghua Yang, Qian Ba and Hui Wang
Journal for ImmunoTherapy of Cancer 2020;8:e000317  (15 March 2020)
Research

Phase 2 study of pembrolizumab in patients with advanced rare cancers

Aung Naing, Funda Meric-Bernstam, Bettzy Stephen, Daniel D Karp, Joud Hajjar, Jordi Rodon Ahnert, Sarina A Piha-Paul, Rivka R Colen, Camilo Jimenez, Kanwal P Raghav, Renata Ferrarotto, Shi-Ming Tu, Matthew Campbell, Linghua Wang, Sarjeel H Sabir, Coya Tapia, Chantale Bernatchez, Michael Frumovitz, Nizar Tannir, Vinod Ravi, Saria Khan, Jeane M Painter, Abulrahman Abonofal, Jing Gong, Anas Alshawa, Lacey M McQuinn, Mingxuan Xu, Sara Ahmed, Vivek Subbiah, David S Hong, Shubham Pant, Timothy A Yap, Apostolia M Tsimberidou, Ecaterina E Ileana Dumbrava, Filip Janku, Siqing Fu, Richard M Simon, Kenneth R Hess, Gauri R Varadhachary and Mouhammed Amir Habra
Journal for ImmunoTherapy of Cancer 2020;8:e000347  (17 March 2020)
Research

PHASE II STUDY OF ALPHA-GALACTOSYLCERMIDE-PULSED ANTIGEN-PRESENTING CELLS IN PATIENTS WITH ADVANCED OR RECURRENT NON-SMALL CELL LUNG CANCER

Takahide Toyoda, Toshiko Kamata, Kazuhisa Tanaka, Fumie Ihara, Mariko Takami, Hidemi Suzuki, Takahiro Nakajima, Takayuki Ikeuchi, Yohei Kawasaki, Hideki Hanaoka, Toshinori Nakayama, Ichiro Yoshino and Shinichiro Motohashi
Journal for ImmunoTherapy of Cancer 2020;8:e000316  (17 March 2020)
Research

Oncolytic vaccinia virus delivering tethered IL-12 enhances antitumor effects with improved safety

Yan Ge, Haiyan Wang, Jinghua Ren, Weilin Liu, Lingjuan Chen, Hongqi Chen, Junjie Ye, Enyong Dai, Congrong Ma, Songguang Ju, Zong Sheng Guo, Zuqiang Liu and David L Bartlett
Journal for ImmunoTherapy of Cancer 2020;8:e000710  (24 March 2020)
Short Report

Survival after checkpoint inhibitors for metastatic acral, mucosal and uveal melanoma

Nicholas D. Klemen, Melinda Wang, Jill C. Rubinstein, Kelly Olino, James Clune, Stephan Ariyan, Charles Cha, Sarah A. Weiss, Harriet M. Kluger and Mario Sznol
Journal for ImmunoTherapy of Cancer 
2020;8:e000341  (24 March 2020)
Short Report

Autophagy induction by thiostrepton improves the efficacy of immunogenic chemotherapy

Yan Wang, Wei Xie, Juliette Humeau, Guo Chen, Peng Liu, Jonathan Pol, Zhen Zhang, Oliver Kepp and Guido Kroemer
Journal for ImmunoTherapy of Cancer 2020;8:e000462 (26 March 2020)
Research

EPCAM-HIGH LIVER CANCER STEM CELLS RESIST NATURAL KILLER CELL-MEDIATED CYTOTOXICITY BY UPREGULATING CEACAM1

Dong Jun Park, Pil Soo Sung, Jung-Hee Kim, Gil Won Lee, Jeong Won Jang, Eun Sun Jung, Si Hyun Bae, Jong Young Choi, and Seung Kew Yoon
Journal for ImmunoTherapy of Cancer 2020;8:e000301  (26 March 2020)
Research

Cellular cytotoxicity is a form of immunogenic cell death

Luna Minute, Alvaro Teijeira, Alfonso R Sanchez-Paulete, Maria C Ochoa, Maite Alvarez, Itziar Otano, Iñaki Etxeberrria, Elixabet Bolaños, Arantza Azpilikueta, Saray Garasa, Noelia Casares, Jose Luis Perez Gracia, Maria E Rodriguez-Ruiz, Pedro Berraondo and Ignacio Melero
Journal for ImmunoTherapy of Cancer 2020;8:e000325 (26 March 2020)
Research

Lactoferrin-containing immunocomplex mediates antitumor effects by resetting tumor-associated macrophages to M1 phenotype

Hongliang Dong, Yueyao Yang, Chenhui Gao, Hehe Sun, Hongmin Wang, Chao Hong, Jun Wang, Fangyuan Gong and Xiaoming Gao
Journal for ImmunoTherapy of Cancer 
2020;8:e000339 (26 March 2020)
Research

CD244 REPRESENTS A NEW THERAPEUTIC TARGET IN HEAD AND NECK SQUAMOUS CELL CARCINOMA

Laura Agresta, Maria Lehn, Kristin Lampe, Rachel Cantrell, Cassandra Hennies, Sara Szabo, Trisha Wise-Draper, Laura Conforti, Kasper Hoebe and Edith M Janssen
Journal for ImmunoTherapy of Cancer 
2020;8:e000245 (26 March 2020)
Research

MULTIFACETED EFFECT OF SOLUBLE HUMAN CD6 IN EXPERIMENTAL CANCER MODELS

Inês T Simões, Fernando Aranda, Sergi Casadó-Llombart, María Velasco-de Andrés, Cristina Català, Pilar Álvarez, Marta Consuegra-Fernández, Marc Orta-Mascaró, Ramón Merino, Jesús Merino, José Alberola-Ila, Gloria González-Aseguinolaza, Esther Carreras, Vanesa Martínez and Francisco Lozano
Journal for ImmunoTherapy of Cancer 
2020;8:e000172 (26 March 2020)
Research

COMPLETE RESPONSE TO ANTI-PD-L1 ANTIBODY IN A METASTATIC BLADDER CANCER ASSOCIATED WITH NOVEL MSH4 MUTATION AND MICROSATELLITE INSTABILITY

Yuanquan Yang, Rohit K Jain, Sean T Glenn, Bo Xu, Prashant K Singh, Lei Wei, Qiang Hu, Mark Long, Nicholas Hutson, Jianming Wang, Sebastiano Battaglia and Saby George
Journal for ImmunoTherapy of Cancer 
2020;8:e000128 (26 March 2020)
Case Report

COMBINED IMMUNOTHERAPY WITH NIVOLUMAB AND IPILIMUMAB WITH AND WITHOUT LOCAL THERAPY IN PATIENTS WITH MELANOMA BRAIN METASTASIS: A DECOG STUDY IN 380 PATIENTS

Teresa Amaral, Felix Kiecker, Sarah Schaefer, Henner Stege, Katharina Kaehler, Patrick Terheyden, Anja Gesierich, Ralf Gutzmer, Sebastian Haferkamp, Jochen Uttikal, Carola Berking, David Rafei-Shamsabadi, Lydia Reinhardt, Friedegund Meier, Ante Karoglan, Christian Posch, Thilo Gambichler, Claudia Pfoehler, Kai Thoms, Julia Tietze, Dirk Debus, Rudolf Herbst, Steffen Emmert, Carmen Loquai, Jessica C Hassel, Frank Meiss, Thomas Tueting, Vanessa Heinrich, Thomas Eigentler, Claus Garbe and Lisa Zimmer
Journal for ImmunoTherapy of Cancer 
2020;8:e000333 (26 March 2020)
Research

PRECLINICAL PET IMAGING OF BISPECIFIC ANTIBODY ERY974 TARGETING CD3 AND GLYPICAN 3 REVEALS THAT TUMOR UPTAKE CORRELATES TO T CELL INFILTRATE

Stijn JH Waaijer, Danique Giesen, Takahiro Ishiguro, Yuji Sano, Naofumi Sugaya, Carolina P Schröder, Elisabeth GE de Vries and Marjolijn N Lub-de Hooge
Journal for ImmunoTherapy of Cancer 
2020;8:e000548 (26 March 2020)
Research

SAFETY AND EFFICACY OF IMMUNE CHECKPOINT INHIBITORS IN ADVANCED UROLOGICAL CANCERS WITH PRE-EXISTING AUTOIMMUNE DISORDERS: A RETROSPECTIVE INTERNATIONAL MULTICENTER STUDY

Nieves Martinez Chanza, Wanling Xie, Majd Issa, Hannah Dzimitrowicz, Abhishek Tripathi, Benoit Beuselinck, Elaine Lam, Yousef Zakharia, Rana Mckay, Sumit Shah, Amir Mortazavi, Michael R. Harrison, Spyridon Sideris, Marina D Kaymakcalan, Sarah Abou Alaiwi, Amin H Nassar, Pier Vitale Nuzzo, Anis Hamid, Toni K Choueiri and Lauren C Harshman
Journal for ImmunoTherapy of Cancer 
2020;8:e000538 (26 March 2020)
Research

IMMUNOSUPPRESSANT INDULGES EBV REACTIVATION AND RELATED LYMPHOPROLIFERATIVE DISEASE BY INHIBITING V-DELTA-2+ T CELLS ACTIVITIES AFTER HEMATOPOIETIC TRANSPLANTATION FOR BLOOD MALIGNANCIES

Jiangying Liu, Haitao Gao, Lan-Ping Xu, Xiao-Dong Mo, Ruoyang Liu, Shuang Liang, Ning Wu, Ming Wang, Zhidong Wang, Ying-Jun Chang, Yu Wang, Xiao-Hui Zhang and Xiao-Jun Huang
Journal for ImmunoTherapy of Cancer 
2020;8:e000208 (26 March 2020)
Research

PERFORMANCE OF ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR T CELLS IN GENETICALLY DEFINED CLASSES OF CHRONIC LYMPHOCYTIC LEUKEMIA

Veronika Mancikova, Helena Peschelova, Veronika Kozlova, Aneta Ledererova, Adriana Ladungova, Jan Verner, Tomas Loja, Frantisek Folber, Jiri Mayer, Sarka Pospisilova and Michal Smida
Journal for ImmunoTherapy of Cancer 
2020;8:e000471 (26 March 2020)
Research

CHARACTERIZATION OF TUMOR MUTATION BURDEN, PD-L1 AND DNA REPAIR GENES TO ASSESS RELATIONSHIP TO IMMUNE CHECKPOINT INHIBITORS RESPONSE IN MATASTATIC RENAL CELL CARCINOMA

Matthew Kyle Labriola, Jason Zhu, Rajan Gupta, Shannon McCall, Jennifer Jackson, Eric F Kong, James R White, Gustavo Cerqueira, Kelly Gerding, John K Simmons, Daniel George and Tian Zhang
Journal for ImmunoTherapy of Cancer 
2020;8:e000319 (26 March 2020)
Research

IDENTIFICATION AND VALIDATION OF DICHOTOMOUS IMMUNE SUBTYPES BASED ON INTRATUMORAL IMMUNE CALLS INFILTRATION IN CLEAR CELL RENAL CELL CARCINOMA PATIENTS

Ying Xiong, Zewei Wang, Quan Zhou, Han Zeng, Hongyu Zhang, Zhaopei Liu, Qiuren Huang, Jiajun Wang, Yuan Chang, Yu Xia, Yiwei Wang, Li Liu, Yu Zhu, Le Xu, Bo Dai, Qi Bai, Jianming Guo and Jiejie Xu
Journal for ImmunoTherapy of Cancer 
2020;8:e000447 (26 March 2020)
Research

ESTABLISHING GUIDELINES TO HARMONIZE TUMOR MUTATIONAL BURDEN (TMB): IN SILICO ASSESSMENT OF VARIATION IN TMB QUANTIFICATION ACROSS DIAGNOSTIC PLATFORMS: PHASE I OF THE FRIENDS OF CANCER RESEARCH TMB HARMONIZATION PROJECT

Diana M Merino, Lisa M McShane, David Fabrizio, Vincent Funari, Shu-Jen Chen, James R White, Paul Wenz, Jonathan Baden, J Carl Barrett, Ruchi Chaudhary, Li Chen, Wangjuh (Sting) Chen, Jen-Hao Cheng, Dinesh Cyanam, Jennifer S Dickey, Vikas Gupta, Matthew Hellmann, Elena Helman, Yali Li, Joerg Maas, Arnaud Papin, Rajesh Patidar, Katie J Quinn, Naiyer Rizvi, Hongseok Tae, Christine Ward, Mingchao Xie, Ahmet Zehir, Chen Zhao, Manfred Dietel, Albrecht Stenzinger, Mark Stewart and Jeff Allen
Journal for ImmunoTherapy of Cancer 
2020;8:e000147 (26 March 2020)
Research

LONGITUDINAL NK CELL KINETICS AND CYTOTOXICITY IN CHILDREN WITH NEUROBLASTOMA ENROLLED IN A CLINICAL PHASE II TRIAL

Rosa Nguyen, Natasha Sahr, April Sykes, Mary Beth McCarville, Sara M Federico, Amanda Sooter, David Cullins, Barbara Rooney, William E Janssen, Aimee C Talleur, Brandon M Triplett, Gwendolyn Anthony, Michael A Dyer, Alberto S Pappo, Wing H Leung and Wayne L Furman
Journal for ImmunoTherapy of Cancer 
2020;8:e000176 (26 March 2020)
Short Report

CHARACTERIZATION OF HUMAN CANCER XENOGRAFTS IN HUMANIZED MICE

Jonathan Rios-Doria, Christina Stevens, Christopher Maddage, Kerri Lasky and Holly K Koblish
Journal for ImmunoTherapy of Cancer 
2020;8:e000416 (26 March 2020)
Short Report

CONDITIONAL IMMUNE TOXICITY RATE IN PATIENTS WITH METASTATIC RENAL AND UROTHELIAL CANCER TREATED WITH IMMUNE CHECKPOINT INHIBITORS

Pier Vitale Nuzzo, Gregory R Pond, Sarah Abou Alaiwi, Amin H Nassar, Ronan Flippot, Catherine Curran, Kerry L Kilbridge, Xiao X Wei, Bradley A McGregor, Toni Choueiri, Lauren C Harshman and Guru Sonpavde
Journal for ImmunoTherapy of Cancer 
2020;8:e000371 (30 March 2020)
Short Report

T CELL RECEPTOR REPERTOIRE CHARACTERISTICS BOTH BEFORE AND FOLLOWING IMMUNOTHERAPY CORRELATE WITH CLINICAL RESPONSE IN MESOTHELIOMA

Heleen Vroman, Giulia Balzaretti, Robert A Belderbos, Paul L Klarenbeek, Menno van Nimwegen, Koen Bezemer, Robin Cornelissen, Ilse T G Niewold, Barbera D van Schaik, Antione H van Kampen, Joachim G J V Aerts, Niek de Vries and Rudi W Hendriks
Journal for ImmunoTherapy of Cancer 
2020;8:e000251 (30 March 2020)
Short Report

LAG3 (LAG-3, CD223) DNA METHYLATION CORRELATES WITH LAG3 EXPRESSION BY TUMOR AND IMMUNE CELLS, IMMUNE CELL INFILTRATION, AND OVERALL SURVIVAL IN CLEAR CELL RENAL CELL CARCINOMA

Niklas Klümper, Damian J Ralser, Emma Grace Bawden, Jenny Landsberg, Romina Zarbl, Glen Kristiansen, Marieta Toma, Manuel Ritter, Michael Hölzel, Jörg Ellinger and Dimo Dietrich
Journal for ImmunoTherapy of Cancer 
2020;8:e000552 (30 March 2020)
Research

SITC Members Receive 50 Percent Submission Discount in 2020

*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 members with a 50 percent discount on processing fees for all JITC articles accepted in 2020.