JITC Digest July 2020

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Inside this Issue:

Letter from the Editor

Dear JITC Readers,pedro-romero_1__1_.jpg

I am thrilled to share exciting news with you in this latest edition of the JITC digest. This year, JITC increased its impact factor to 9.913, making the journal the highest ranked fully open access immunology journal and in the top 8 percent of all journals in the oncology and immunology categories. The ranking not only reflects the increasing prominence of the cancer immunotherapy field as a whole, but also the outstanding efforts of our JITC editors and expert reviewers, who work tirelessly to ensure that the journal publishes only the top-tier submissions month after month. With a sharp increase in manuscripts submitted to JITC during the last two years, we remain committed to a high standard of timely peer review and to facilitating the publishing of high quality content for our readership.
 
This month is no exception, with a total of 63 articles publishing in JITC during June. As always, the research spans a wide diversity of topics representing almost every step in the path from bench to bedside. The papers highlighted in this month’s digest include basic research, translational science and human trials.
 
On the basic science side, Lorena Carmona Rodríguez and colleagues uncover a novel, cell context-specific role for WNT signaling in controlling access to tumors by infiltrating lymphocytes. In another study investigating changes to the tumor microenvironment, Simon P Keam et al demonstrate through NanoString immune gene expression profiling, digital spatial profiling, and high-throughput immune cell multiplex immunohistochemistry analysis on samples from human patients, that high dose-rate brachytherapy converts immunologically cold tumors to hot.
 
On the therapeutics side, Matteo Libero Baroni et al provide evidence that CD123-directed chimeric antigen receptor T cells are profoundly myeloablative, opening the door to a potential bridge to transplant therapy for acute myeloid leukemia. Victoria A Brentvile and colleagues develop a novel tumor vaccine based on a mixture of three citrullinated peptides that takes advantage of a toll-like receptor agonist adjuvant to dramatically reduce the effective therapeutic dose. Additionally, Adi Reches and colleagues identify a potentially promising new target for checkpoint inhibition in Nectin4, which is a TIGIT ligand with highly restricted expression to tumor cells.
 
Finally, David S Hong and colleagues demonstrate significant increases in tumor-infiltrating CD3+ and CD8+ T cells in patients with advanced solid tumors after treatment with a small-molecule antagonist of the E-type prostanoid receptor 4 in a first-in-human clinical trial.
 
I hope you enjoy these articles, and all of the excellent papers published this month in JITC. Also, be sure to peruse this month’s JITC's Reading List for a selection of papers of interest from other journals.
 
Best regards,

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


JITC Editor Picks

SOD3 induces a HIF-2 alpha-dependent program in endothelial cells that provides a selective signal for tumor infiltration by T cells

Lorena Carmona-Rodríguez, Diego Martínez-Rey, Maria Jesús Fernández-Aceñero, Alicia González-Martín, Mateo Paz-Cabezas, Noe Rodríguez-Rodríguez, Beatriz Pérez-Villamil, Maria Eugenia Sáez, Eduardo Díaz-Rubio, Emilia Mira, Santos Mañes
Journal for ImmunoTherapy of Cancer 2020;8:e000432 (25 June 2020)
Research

Summary:

Tumors exclude infiltrating lymphocytes by cell-intrinsic and extrinsic mechanisms, including aberrant activation of the WNT/beta-catenin pathway and vascular dysfunction. Lorena Carmona Rodríguez et al identify a new mechanism that regulates immune cell infiltration into tumors, centered around SOD3. Overexpression of SOD3 in endothelial cells increased CD3+ T cell adhesion and transmigration in vitro for both naïve and ex vivo activated cells. In mice bearing LLC tumors, overexpression of SOD3 in the tumor microenvironment via either the administration of an adenoviral vector or lovastatin led to delayed tumor growth and extended survival, but only when the animals were first treated with doxorubicin to induce immunogenic cell death. In adoptive transfer experiments, the numbers of tumor-infiltrating lymphocytes correlated with tumor control. Overexpression of SOD3 did not lead to any significant changes in chemokine levels in the supernatants of cultured cells or in tumors in vivo. Downstream of SOD3, endothelial overexpression of HIF-2 alpha enhanced transmigration of CD4+ and CD8+ T cells in vitro. Compartment-specific knockout of HIF-2 alpha in endothelial cells led to reduced tumor T cell infiltration and eliminated the effects of SOD3 overexpression on tumor control. Both in vitro and in vivo, HIF-2 alpha silencing reduced expression of WISP2 mRNA, which encodes a non-conventional WNT ligand. Expression of the WNT-regulated basement membrane component LAMA4 was also induced by SOD3 in vitro and in vivo. Analysis of a tissue microarray of 95 primary stage II colorectal carcinomas showed that SOD3 positivity was associated with enhanced endothelial WNT signaling, increased LAM4 staining in neoplastic and stromal cells and CD8+ T cell density. The results highlight the basement membrane as a potential new target to promote immune cell infiltration to enhance anti-tumor responses.

High dose-rate brachytherapy of localized prostate cancer converts tumors from cold to hot

Simon P Keam, Heloise Halse, Thu Nguyen, Minyu Wang, Nicolas Van Kooten Losio, Catherine Mitchell, Franco Caramia, David J Byrne, Sue Haupt, Georgina Ryland, Phillip K Darcy, Shahneen Sandhu, Piers Blombery, Ygal Haupt, Scott G Williams, Paul J Neeson.
Journal for ImmunoTherapy of Cancer 2020;8:e000792  (24 June 2020)

Research

Summary:

Localized prostate cancer has a profoundly immunosuppressed phenotype with tumor-associated lymphocytes present only at the margins and excluded from within the tumor. To determine whether the standard curative intent treatment, high dose-rate brachytherapy (HDRBT) alters prostate immune context, Simon P Keam et al performed NanoString immune gene expression profiling, digital spatial profiling, and high-throughput immune cell multiplex immunohistochemistry analysis on pre- and post-radiation tissue samples from a cohort of 24 patients. Using the NanoString nCounter PanCancer Immune Profiling platform, 59 highly significant genes were differentially expressed after HDRBT, a response that was diverse and included innate, humoral, adaptive, and inflammatory immunity. Digital spatial profiling revealed that the HDRBT-induced inflammatory signature was broadly driven by a mix of infiltrative immune cells includes CD8+ T cells, Tregs, macrophages, and dendritic cells. Additionally, several immune checkpoint molecules were significantly upregulated after HDRBT. Although the overall density of immune cell subsets in the prostate as a whole was not affected by radiation, in tumor zones, both Tregs and CD4+ T cells were more associated with PD-L1+ HMWCK- cells after HDBRT while the interaction of PD-L1- dendritic cells with their PD-L1+ counterparts and with PD-L1+ macrophages and B cells was preferentially lost. In multivariate analysis, the main spatial response to radiation that drove inflammatory gene expression response was a decrease in distance between T cells and dendritic cells and macrophages and dendritic cells in both tumor and nontumor zones. The findings suggest that HDBRT could perturb the tumor microenvironment in such a way that immunotherapy may improve outcomes in prostate cancer patients.

41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo

Matteo Libero Baroni, Diego Sanchez Martinez, Francisco Gutierrez Aguera, Heleia Roca Ho, Maria Castella, Samanta Romina Zanetti, Talia Velasco Hernandez, Rafael Diaz de la Guardia, Julio Castaño, Eduardo Anguita, Susana Vives, Josep Nomdedeu, Helene Lapillone, Anne E Bras, Vincent H J van der Velden, Jordi Junca, Pedro Marin, Alex Bataller, Jordi Esteve, Binje Vick, Irmela Jeremias, Angel Lopez, Marc Sorigue, Clara Bueno, Pablo Menendez
Journal for ImmunoTherapy of Cancer 2020;8:e000845 (10 June 2020)
Research

Summary:

The development of chimeric antigen receptor (CAR) T cell immunotherapies for acute myeloid leukemia (AML) has been hindered by both highly heterogeneous expression of target antigens on malignant cells and shared expression of target antigens with normal hematopoietic stem/progenitor cells (HSPCs). To identify a viable target for AML immunotherapy, Matteo Libero Baroni and colleagues analyzed 97 primary samples both from the time of diagnosis and at relapse and found that CD123 was the most common and homogeneously expressed antigen. Patient-derived CD3+ T cells could be successfully transfected with lentiviral vectors carrying second generation anti-CD123 CARs, and the resulting manufactured CAR T cells generated high levels of proinflammatory cytokines IL-2, TNF-alpha and IFN-gamma when cocultured with AML cell lines regardless if they were based on a CD28 or a 41BB costimulatory domain. Importantly, though, both CD28- and 41BB-based anti-CD123 CAR T cells were profoundly myeloablative in vitro. In xenograft models, anti-CD123 CAR T cells controlled disease while also hampering the viability and clonogenic capacity of CD34+ HSPCs. In xenograft models of human engraftment in the presence of existing hematopoiesis, CD28-based CD123 CARTs proved less myeloablative than 41BB-CD123 CARTs. Both costimulatory domains, however, prevented healthy hematopoietic reconstitution in models of de novo engraftment of HSPCs. The findings emphasize a need for caution when clinically implementing CD123 CAR T cell therapies.

Combination vaccine based on citrullinated vimentin and enolase peptides induces potent CD4-mediated anti-tumor responses

Victoria A Brentville, Rachael L Metheringham, Ian Daniels, Suha Atabani, Peter Symonds, Katherine W Cook, Mireille Vankemmelbeke, Ruhul Choudhury, Poonam Vaghela, Mohamed Gijon, Ghislaine Meiners, Willem-Jan Krebber, Cornelis J M Melief, Lindy G Durrant
Journal for ImmunoTherapy of Cancer 2020;8:e000560 (18 June 2020)

Research

Summary:

Under conditions of cellular stress such as occurs within tumors, citrullination within the autophagosome can lead to new epitopes that elicit robust T cell responses when presented by MHC class II. To develop novel antigens, Victoria A Brentville and colleagues created a vaccine based on a combination of three citrullinated peptides: two derived from vimentin and one derived from enolase. In HLA-transgenic mice, vaccination with the mixture elicited high-frequency peptide specific responses with no evidence of immunodominance for one antigen over any other. Vaccination of melanoma and ovarian tumor-bearing mice led to regression, and responses were more pronounced when the peptide mixture was combined with a TLR9/TLR4 adjuvant. Additionally, vaccination protected against rechallenge. Tumor regression after vaccination correlated with increases in infiltrating CD4+ T cells and decreases in myeloid-derived suppressor cells. Depletion of CD4+ T cells eliminated the antitumor effects of the vaccine. A variety of adjuvants, including TLR9/TLR4, TLR3, GM-CSF and TLR2 agonists, elicited high frequencies of citrullinated peptide-specific T cells after vaccination. Linking a TLR1/2 agonist allowed for the vaccine to confer a significant survival advantage in an aggressive model of melanoma in mice, even at 100-fold lower doses than previously used. In PBMCs from ovarian cancer patients, the vaccine peptides elicited CD4+ T cell proliferative responses and interferon gamma and granzyme B expression. The study makes a case for further translation of the citrullinated peptide vaccine into the clinic.

Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity

Adi Reches, Yael Ophir, Natan Stein, Inbal Kol, Batya Isaacson, Yoav Charpak Amikam, Afek Elnekave, Pinchas Tsukerman, Paola Kucan Brlic, Tihana Lenac, Barbara Seliger, Stipan Jonjic, Ofer Mandelboim
Journal for ImmunoTherapy of Cancer 2020;8:e000266 (5 June 2020)

Research

Summary:

Several investigational checkpoint inhibitors targeting the T-cell immunoreceptor with Ig and ITIM domains (TIGIT) have entered clinical trials. Adi Reches and colleagues identify a potentially promising new target for checkpoint inhibition in Nectin4, a novel TIGIT ligand with strictly restricted expression that is limited to tumor cells. Nectin4 showed similar in vitro binding affinity to TIGIT as PVR as measured by microscale thermophoresis, and the ligand-receptor interaction led to reduced cytotoxicity in primary human natural killer (NK) cells. In mice implanted with Nectin4 overexpressing Raji cells (a transfectable human lymphoblastoid cell line derived from a patient with Burkitt’s lymphoma) and human NK cells, administration of anti-Nectin4 monoclonal antibodies slowed tumor growth. The anti-Nectin4 antibodies also slowed tumor growth when mice were implanted with human NK cells and MDA-MB-453 tumors (which are derived from breast cancer and express Nectin4 along with additional ligands in the Nectin family). Analysis of gene expression data from lung adenocarcinoma patients and colon cancer patients revealed that high Nectin4 expression was associated with worse overall survival. Targeting Nectin4 may prove to be an effective strategy for cancer immunotherapy with less likelihood of immune-related adverse events.

First-in-human phase I study of immunomodulatory E7046, an antagonist of PGE2-receptor E-type 4 (EP4), in patients with advanced cancers

David S Hong, Aparna Parikh, Geoffrey I Shapiro, Andrea Varga, Aung Naing, Funda Meric-Bernstam, Özlem Ataman, Larisa Reyderman, Terri A Binder, Min Ren, Mingjie Liu, Satish Dayal, Amy Y Siu, Pallavi Sachdev, Lucy Xu, Vijay Bhagawati-Prasad, Ilian Tchakov, Chean Eng Ooi, Xingfeng Bao, Aurelien Marabelle
Journal for ImmunoTherapy of Cancer 2020;8:e000222 (17 June 2020)

Research

Summary:

Tumors exploit the effects of prostaglandins on monocytic cell differentiation and T cell activation in order to maintain an immunosuppressive microenvironment. Based on pre-clinical evidence that E7046, a highly selective, small-molecule antagonist of the E-type prostanoid receptor 4 (EP4), inhibited the growth of multiple mouse syngeneic tumor models, David S Hong and colleagues enrolled 30 patients with advanced tumors of cancer types associated with high levels of myeloid infiltrates in a first-in-human clinical trial. E7046 was administered orally once-daily in sequential escalating dose cohorts with 6 or more patients per cohort. No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached. Treatment-related adverse events (AEs) occurred in 16 patients (53%) and grade 3 or higher treatment-related AEs occurred in three patients (10%). No objective responses were observed by irRECIST—stable disease was observed in seven patients (23%), and the disease control rate was 23%. Stable disease was observed across several dose levels examined, and exposure to study drug increased dose proportionally up to 500 mg. Paired tumor biopsies before treatment and on cycle 2 day 1 revealed significant increases in CD3+ and CD8+ T cells as well as changes in the levels of key EP4-regulated genes, including upregulation of tumor necrosis factor alpha and C-X-C motif chemokine ligand 10 (CXCL10), although the increases did not reach statistical significance. Serum levels of the T cell recruiting cytokines CXCL10 and C-C motif chemokine ligand 5 (CCL5) were significantly upregulated on treatment. The study shows that E7046 treatment was associated with manageable toxicity. Two doses, 250 mg and 500 mg, were chosen as the recommended phase II dose for future clinical investigation.

TFEB is a master regulator of tumor-associated macrophages in breast cancer

Yong Li, Johnie Hodge, Qing Liu, Junfeng Wang, Yuzhen Wang, Trent D Evans, Diego Altomare, Yongzhong Yao, E Angela Murphy, Babak Razani, Daping Fan
Journal for ImmunoTherapy of Cancer 
2020;8:e000543 (2 June 2020)
Research

Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase II study

Kaichao Feng, Yang Liu, Yongtian Zhao, Qingming Yang, Liang Dong, Jiejie Liu, Xiang Li, Zhikun Zhao, Qian Mei, Weidong Han
Journal for ImmunoTherapy of Cancer 
2020;8:e000367 (2 June 2020)
Research

Restoration of miR-340 controls pancreatic cancer cell CD47 expression to promote macrophage phagocytosis and enhance antitumor immunity

Qing Xi, Jieyou Zhang, Guangze Yang, Lijuan Zhang, Ying Chen, Chengzhi Wang, Zimu Zhang, Xiangdong Guo, Jingyi Zhao, Zhenyi Xue, Yan Li, Qi Zhang, Yurong Da, Li Liu, Zhi Yao, Rongxin Zhang
Journal for ImmunoTherapy of Cancer 
2020;8:e000253 (4 June 2020)
Research

Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients

Megan H Trager, Shana M Coley, Geoffrey Dube, Shaheer Khan, Matthew Ingham, Faramarz H Samie, Larisa J Geskin, Diana McDonnell, Daniel Brouder, Yvonne Saenger, Richard Carvajal
Journal for ImmunoTherapy of Cancer 2020;8:e000908  (4 June 2020)
Case Report

Overall survival at 5 years of follow-up in a phase III trial comparing ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma

Paolo Antonio Ascierto, Michele Del Vecchio, Andrzej Mackiewicz, Caroline Robert, Vanna Chiarion-Sileni, Ana Arance, Céleste Lebbé, Inge Marie Svane, Catriona McNeil, Piotr Rutkowski, Carmen Loquai, Laurent Mortier, Omid Hamid, Lars Bastholt, Brigitte Dreno, Dirk Schadendorf, Claus Garbe, Marta Nyakas, Jean-Jacques Grob, Luc Thomas, Gabriella Liszkay, Michael Smylie, Christoph Hoeller, Virginia Ferraresi, Florent Grange, Ralf Gutzmer, Joanna Pikiel, Fareeda Hosein, Burcin Simsek, Michele Maio
Journal for ImmunoTherapy of Cancer 2020;8:e000391  (4 June 2020)
Research

Early tumor shrinkage identifies long-term disease control and survival in patients with lung cancer treated with atezolizumab

Ashley M Hopkins, Ganessan Kichenadasse, Chris S Karapetis, Andrew Rowland, Michael J Sorich
Journal for ImmunoTherapy of Cancer 2020;8:e000500  (4 June 2020)
Research

Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial

Dmitriy Zamarin, Sven Walderich, Aliya Holland, Qin Zhou, Alexia E Iasonos, Jean M Torrisi, Taha Merghoub, Lewis F Chesebrough, Autumn S Mcdonnell, Jacqueline M Gallagher, Yanyun Li, Travis J Hollmann, Rachel N Grisham, Courtney L Erskine, Mathew S Block, Keith L Knutson, Roisin E O’Cearbhaill, Carol Aghajanian, Jason A Konner
Journal for ImmunoTherapy of Cancer 2020;8:e000829  (4 June 2020)
Clinical Trials Monitor

Circulating CD14high CD16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression

Mélissa Prat, Augustin Le Naour, Kimberley Coulson, Fanny Lemée, Hélène Leray, Godefroy Jacquemin, Mouna Chirine Rahabi, Léa Lemaitre, Hélène Authier, Gwenaël Ferron, Jean-Marc Barret, Alejandra Martinez, Maha Ayyoub, Jean-Pierre Delord, Laurence Gladieff, Isabelle Tabah-Fisch, Jean-François Prost, Bettina Couderc, Agnès Coste
Journal for ImmunoTherapy of Cancer 
2020;8:e000472 (4 June 2020)
Short Report

Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein

Nicolas Torres, María Victoria Regge, Florencia Secchiari, Adrián David Friedrich, Raúl Germán Spallanzani, Ximena Lucía Raffo Iraolagoitia, Sol Yanel Núñez, Jessica Mariel Sierra, Andrea Ziblat, María Cecilia Santilli, Nicolás Gilio, Evangelina Almada, Constanza Lauche, Romina Pardo, Carolina Inés Domaica, Mercedes Beatriz Fuertes, Kevin Patrick Madauss, Kenneth W Hance, Israel S Gloger, Vanesa Zylberman, Fernando Alberto Goldbaum, Norberto Walter Zwirner
Journal for ImmunoTherapy of Cancer 2020;8:e000233  (8 June 2020)
Research

Nanopore sequencing as a scalable, cost-effective platform for analyzing polyclonal vector integration sites following clinical T cell therapy

Ping Zhang, Devika Ganesamoorthy, Son Hoang Nguyen, Raymond Au, Lachlan J Coin, Siok-Keen Tey
Journal for ImmunoTherapy of Cancer 2020;8:e000299  (10 June 2020)
Research

CD103+ tumor-resident CD8+ T cell numbers underlie improved patient survival in oropharyngeal squamous cell carcinoma

Rehana Hewavisenti, Angela Ferguson, Kevin Wang, Deanna Jones, Thomas Gebhardt, Jarem Edwards, Mei Zhang, Warwick Britton, Jean Yang, Angela Hong, Umaimainthan Palendira
Journal for ImmunoTherapy of Cancer 2020;8:e000452  (10 June 2020)
Short Report

Identification of PD1-mediated regulation of antitumor antigen response in patients with NSCLC using the trans vivo DTH assay

Diego A Lema, Ewa Jankowska-Gan, Nan Sethakorn, William Burlingham, Ticiana Leal
Journal for ImmunoTherapy of Cancer 2020;8:e000152  (10 June 2020)
Short Report

Rechallenge patients with immune checkpoint inhibitors following severe immune-related adverse events: review of the literature and suggested prophylactic strategy

John Haanen, Marc Ernstoff, Yinghong Wang, Alexander Menzies, Igor Puzanov, Petros Grivas, James Larkin, Solange Peters, John Thompson, Michel Obeid
Journal for ImmunoTherapy of Cancer 2020;8:e000604  (12 June 2020)
Commentary

HER2-LAMP vaccines effectively traffic to endolysosomal compartments and generate enhanced polyfunctional T cell responses that induce complete tumor regression

Alan Chen Chen, Renhuan Xu, Tao Wang, Junping Wei, Xiao-Yi Yang, Cong-Xiao Liu, Gangjun Lei, Herbert Kim Lyerly, Teri Heiland, Zachary Conrad Hartman
Journal for ImmunoTherapy of Cancer 
2020;8:e000258  (12 June 2020)
Research

IL-15 superagonist RLI has potent immunostimulatory properties on NK cells: implications for antimetastatic treatment

Mélanie Desbois, Coralie Béal, Mélinda Charrier, Benjamin Besse, Guillaume Meurice, Nicolas Cagnard, Yannick Jacques, David Béchard, Lydie Cassard, Nathalie Chaput
Journal for ImmunoTherapy of Cancer 
2020;8:e000632 (12 June 2020)
Research

Stromal LAG-3+ cells infiltration defines poor prognosis subtype muscle-invasive bladder cancer with immunoevasive contexture

Han Zeng, Quan Zhou, Zewei Wang, Hongyu Zhang, Zhaopei Liu, Qiuren Huang, Jiajun Wang, Yuan Chang, Qi Bai, Yu Xia, Yiwei Wang, Le Xu, Bo Dai, Jianming Guo, Li Liu, Yu Zhu, Jiejie Xu
Journal for ImmunoTherapy of Cancer 
2020;8:e000651 (14 June 2020)
Research

Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors

Jayesh Desai, Sanjeev Deva, Jong Seok Lee, Chia-Chi Lin, Chia-Jui Yen, Yee Chao, Bhumsuk Keam, Michael Jameson, Ming-Mo Hou, Yoon-Koo Kang, Ben Markman, Chang-Hsien Lu, Kun-Ming Rau, Kyung-Hun Lee, Lisa Horvath, Michael Friedlander, Andrew Hill, Shahneen Sandhu, Paula Barlow, Chi-Yuan Wu, Yun Zhang, Liang Liang, John Wu, Virginia Paton, Michael Millward
Journal for ImmunoTherapy of Cancer 
2020;8:e000453 (15 June 2020)
Research

Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing

Danny Rischin, Michael R Migden, Annette M Lim, Chrysalyne D Schmults, Nikhil I Khushalani, Brett G M Hughes, Dirk Schadendorf, Lara A Dunn, Leonel Hernandez-Aya, Anne Lynn S Chang, Badri Modi, Axel Hauschild, Claas Ulrich, Thomas Eigentler, Brian Stein, Anna C Pavlick, Jessica L Geiger, Ralf Gutzmer, Murad Alam, Emmanuel Okoye, Melissa Mathias, Vladimir Jankovic, Elizabeth Stankevich, Jocelyn Booth, Siyu Li, Israel Lowy, Matthew G Fury, Alexander Guminski
Journal for ImmunoTherapy of Cancer
 
2020;8:e000775  (17 June 2020)
Research

Immunomodulation to enhance the efficacy of an HPV therapeutic vaccine

Claire Smalley Rumfield, Samuel T Pellom, Y Maurice Morillon II, Jeffrey Schlom, Caroline Jochems
Journal for ImmunoTherapy of Cancer 2020;8:e000612  (17 June 2020)
Research

Combined DLL3-targeted bispecific antibody with PD-1 inhibition is efficient to suppress small cell lung cancer growth

Xin Chen, Norhan Amar, Yuankui Zhu, Chunguang Wang, Chunjiao Xia, Xiaoqing Yang, Dongde Wu, Mingqian Feng
Journal for ImmunoTherapy of Cancer 2020;8:e000785  (17 June 2020)
Research

HDAC9 deficiency promotes tumor progression by decreasing the CD8+ dendritic cell infiltration of the tumor microenvironment

Yongling Ning, Jun Ding, Xiao Sun, Yewen Xie, Mingming Su, Chenglong Ma, Jie Pan, Jie Chen, Hua Jiang, Chunjian Qi
Journal for ImmunoTherapy of Cancer 2020;8:e000529  (17 June 2020)
Research

FC-gamma-RII (CD32) modulates antibody clearance in NOD SCID mice leading to impaired antibody-mediated tumor cell deletion

Robert J Oldham, C Ian Mockridge, Sonya James, Patrick J Duriez, H T Claude Chan, Kerry L Cox, Vicentiu A Pitic, Martin J Glennie, Mark S Cragg
Journal for ImmunoTherapy of Cancer 2020;8:e000619  (17 June 2020)
Research

Distinctive germline expression of class I human leukocyte antigen (HLA) alleles and DRB1 heterozygosis predict the outcome of patients with non-small cell lung cancer receiving PD-1/PD-L1 immune checkpoint blockade

Pierpaolo Correale, Rita Emilena Saladino, Diana Giannarelli, Rocco Giannicola, Rita Agostino, Nicoletta Staropoli, Alessandra Strangio, Teresa Del Giudice, Valerio Nardone, Maria Altomonte, Pierpaolo Pastina, Paolo Tini, Antonia Consuelo Falzea, Natale Imbesi, Valentina Arcati, Giuseppa Romeo, Daniele Caracciolo, Amalia Luce, Michele Caraglia, Antonio Giordano, Luigi Pirtoli, Alois Necas, Evzen Amler, Vito Barbieri, Pierfrancesco Tassone, Pierosandro Tagliaferri
Journal for ImmunoTherapy of Cancer 
2020;8:e000733 (17 June 2020)
Research

Immune-related (IR)-pneumonitis during the COVID-19 pandemic: multidisciplinary recommendations for diagnosis and management

Jarushka Naidoo, Joshua E Reuss, Karthik Suresh, David Feller-Kopman, Patrick M Forde, Seema Mehta Steinke, Clare Rock, Douglas B Johnson, Mizuki Nishino, Julie R Brahmer
Journal for ImmunoTherapy of Cancer 
2020;8:e000984 (17 June 2020)
Article

Cancer Moonshot Immuno-Oncology Translational Network (IOTN): accelerating the clinical translation of basic discoveries for improving immunotherapy and immunoprevention of cancer

Ananth Annapragada, Andrew Sikora, Catherine Bollard, Jose Conejo-Garcia, Conrad Russell Cruz, Shadmehr Demehri, Michael Demetriou, Levon Demirdjian, Lawrence Fong, Mary Horowitz, Alan Hutson, Kathryn Kadash-Edmondson, Donald Kufe, Steven Lipkin, Song Liu, Claire McCarthy, Martin Morgan, Zachary Morris, Yang Pan, Marcelo Pasquini, Stephen Schoenberger, Eliezer Van Allen, Eduardo Vilar, Yi Xing, Wenjuan Zha, the IOTN Consortium, Adekunle Odunsi
Journal for ImmunoTherapy of Cancer 2020;8:e000796 (17 June 2020)
Review

Chronic immune checkpoint inhibitor pneumonitis

Jarushka Naidoo, Tricia R Cottrell, Evan J Lipson, Patrick M Forde, Peter B Illei, Lonny B Yarmus, K Ranh Voong, David Feller-Kopman, Hans Lee, Joanne Riemer, Daphne Wang, Janis M Taube, Julie R Brahmer, Cheng Ting Lin, Sonye K Danoff, Franco R D'Alessio, Karthik Suresh
Journal for ImmunoTherapy of Cancer 
2020;8:e000840 (17 June 2020)
Short Report

Role of the anatomic site in the association of HLA class I antigen expression level in metastases with clinical response to ipilimumab therapy in patients with melanoma

ndrea Ladányi, Eszter Papp, Anita Mohos, Tímea Balatoni, Gabriella Liszkay, Judit Oláh, Anita Varga, Zsuzsanna Lengyel, Gabriella Emri, Soldano Ferrone
Journal for ImmunoTherapy of Cancer 
2020;8:e000209 (17 June 2020)
Short Report

Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study

HLin Shen, Jun Guo, Qingyuan Zhang, Hongming Pan, Ying Yuan, Yuxian Bai, Tianshu Liu, Qing Zhou, Jun Zhao, Yongqian Shu, Xiaoming Huang, Siyang Wang, Jie Wang, Aiping Zhou, Dingwei Ye, Ting Sun, Yujuan Gao, Silu Yang, Zoubai Wang, Jian Li, Yi-Long Wu
Journal for ImmunoTherapy of Cancer 
2020;8:e000437 (18 June 2020)
Research

Fetal exposure to oncoantigen elicited antigen-specific adaptive immunity against tumorigenesis

Jeng-Chang Chen, Liang-Shiou Ou, Ming-Ling Kuo, Li-Yun Tseng, Hsueh-Ling Chang
Journal for ImmunoTherapy of Cancer 2020;8:e000137  (18 June 2020)
Research

Dual oxidase 1 limits the IFN-gamma-associated antitumor effect of macrophages

Lydia Meziani, Marine Gerbé de Thoré, Pauline Hamon, Sophie Bockel, Ruy Andrade Louzada, Céline Clemenson, Raphaël Corre, Wincgygn Liu, Corinne Dupuy, Michele Mondini, Eric Deutsch
Journal for ImmunoTherapy of Cancer 2020;8:e000622  (21 June 2020)
Research

DNA damage repair pathway alterations in metastatic clear cell renal cell carcinoma and implications on systemic therapy

Yasser Ged, Joshua L Chaim, Renzo G DiNatale, Andrea Knezevic, Ritesh R Kotecha, Maria I Carlo, Chung-Han Lee, Ashley Foster, Darren R Feldman, Min Yuen Teo, Gopakumar Iyer, Timothy Chan, Sujata Patil, Robert J Motzer, A Ari Hakimi, Martin H Voss
Journal for ImmunoTherapy of Cancer 2020;8:e000230  (21 June 2020)
Research

Nivolumab-induced synovitis is characterized by florid T cell infiltration and rapid resolution with synovial biopsy-guided therapy

William Murray-Brown, Tom D Wilsdon, Helen Weedon, Susanna Proudman, Shawgi Sukumaran, Sonja Klebe, Jennifer G Walker, Malcolm D Smith, Mihir D Wechalekar
Journal for ImmunoTherapy of Cancer 2020;8:e000281  (21 June 2020)
Case Report

Targeting the coding sequence: opposing roles in regulating classical and non-classical MHC class I molecules by miR-16 and miR-744

Michael Friedrich, Christoforos K Vaxevanis, Katharina Biehl, Anja Mueller, Barbara Seliger
Journal for ImmunoTherapy of Cancer 
2020;8:e000396 (21 June 2020)
Research

Pickering emulsions with ethiodized oil and nanoparticles for slow release of intratumoral anti-CTLA4 immune checkpoint antibodies

Lambros Tselikas, Thierry de Baere, Thomas Isoardo, Sandrine Susini, Karine Ser-Le Roux, Mélanie Polrot, Julien Adam, Mathieu Rouanne, Laurence Zitvogel, Laurence Moine, Fréderic Deschamps, Aurélien Marabelle
Journal for ImmunoTherapy of Cancer 2020;8:e000579  (21 June 2020)
Research

Influence of gut microbiome on multiple myeloma: friend or foe?

Nausheen Ahmed, Mahmoud Ghannoum, Molly Gallogly, Marcos de Lima, Ehsan Malek
Journal for ImmunoTherapy of Cancer 2020;8:e000576  (23 June 2020)
Commentary

Serum interleukin-6 and C-reactive protein are associated with survival in melanoma patients receiving immune checkpoint inhibition

ndressa S Laino, David Woods, Melinda Vassallo, Xiaozhong Qian, Hao Tang, Megan Wind-Rotolo, Jeffrey Weber
Journal for ImmunoTherapy of Cancer 2020;8:e000842  (23 June 2020)
Research

Small cell transformation of non-small cell lung cancer on immune checkpoint inhibitors: uncommon or under-recognized?

Kartik Sehgal, Andreas Varkaris, Hollis Viray, Paul A VanderLaan, Deepa Rangachari, Daniel B Costa
Journal for ImmunoTherapy of Cancer 2020;8:e000697  (23 June 2020)
Case Report

Hyperprogression to camrelizumab in a patient with esophageal squamous cell carcinoma harboring EGFR kinase domain duplication

Wei Wang, Meihong Wu, Minglu Liu, Zhengqing Yan, Guoqiang Wang, Dongliang Mao, Mei Wang
Journal for ImmunoTherapy of Cancer 2020;8:e000793  (23 June 2020)
Case Report

CD200 promotes immunosuppression in the pancreatic tumor microenvironment

Fouad Choueiry, Molly Torok, Reena Shakya, Kriti Agrawal, Anna Deems, Brooke Benner, Alice Hinton, Jami Shaffer, Bradley W Blaser, Anne M Noonan, Terence M Williams, Mary Dillhoff, Darwin L Conwell, Phil A Hart, Zobeida Cruz-Monserrate, Xue-Feng Bai, William E Carson III, Thomas A Mace
Journal for ImmunoTherapy of Cancer 
2020;8:e000189  (23 June 2020)
Research

MRI of tumor T cell infiltration in response to checkpoint inhibitor therapy

Xiaoyu Jiang, Stephanie Dudzinski, Kathryn E Beckermann, Kirsten Young, Eliot McKinley, Oliver J McIntyre, Jeffrey C Rathmell, Junzhong Xu, John C Gore
Journal for ImmunoTherapy of Cancer 
2020;8:e000328  (23 June 2020)
Research

CD3xCD19 DART molecule treatment induces non-apoptotic killing and is efficient against high-risk chemotherapy and venetoclax-resistant chronic lymphocytic leukemia cells

Anne W J Martens, Susanne R Janssen, Ingrid A M Derks, Homer C Adams III, Liat Izhak, Roel van Kampen, Sanne H Tonino, Eric Eldering, Gerritje J W van der Windt, Arnon P Kater
Journal for ImmunoTherapy of Cancer 
2020;8:e000218  (24 June 2020)
Research

Initial dose of oncolytic myxoma virus programs durable antitumor immunity independent of in vivo viral replication

Erica B Flores, Bulent A Aksoy, Eric Bartee
Journal for ImmunoTherapy of Cancer 
2020;8:e000804  (24 June 2020)
Research

Combination treatment with radiotherapy and a novel oxidative phosphorylation inhibitor overcomes PD-1 resistance and enhances antitumor immunity

Dawei Chen, Hampartsoum B Barsoumian, Grant Fischer, Liangpeng Yang, Vivek Verma, Ahmed I Younes, Yun Hu, Fatemeh Masropour, Katherine Klein, Christopher Vellano, Joseph Marszalek, Michael Davies, Maria Angelica Cortez, James Welsh
Journal for ImmunoTherapy of Cancer 
2020;8:e000289  (24 June 2020)
Research

Ipilimumab plus nivolumab for patients with metastatic uveal melanoma: a multicenter, retrospective study

Yana G Najjar, Kristina Navrazhina, Fei Ding, Roma Bhatia, Katy Tsai, Kelly Abbate, Barbara Durden, Zeynep Eroglu, Shailender Bhatia, Song Park, Akansha Chowdhary, Sunandana Chandra, Jonathan Kennedy, Marc Ernstoff, Pankit Vachhani, Joseph Drabick, Arun Singh, Tan Xu, Jessica Yang, Richard Carvajal, Daniel Manson, John M Kirkwood, Justine Cohen, Ryan Sullivan, Douglas Johnson, Pauline Funchain, Alexander Shoushtari
Journal for ImmunoTherapy of Cancer 
2020;8:e000331  (24 June 2020)
Research

Sequential ctDNA whole-exome sequencing in advanced lung adenocarcinoma with initial durable tumor response on immune checkpoint inhibitor and late progression

Etienne Giroux Leprieur, Zofia Hélias-Rodzewicz, Paul Takam Kamga, Adrien Costantini, Catherine Julie, Alexandre Corjon, Coraline Dumenil, Jennifer Dumoulin, Violaine Giraud, Sylvie Labrune, Simon Garinet, Thierry Chinet, Jean-François Emile
Journal for ImmunoTherapy of Cancer 
2020;8:e000527  (24 June 2020)
Research

Immune checkpoint inhibitor-associated celiac disease

Yousef R Badran, Angela Shih, Donna Leet, Meghan J Mooradian, Alexandra Coromilas, Jonathan Chen, Marina Kem, Hui Zheng, Jennifer Borowsky, Joseph Misdraji, Mari Mino-Kenudson, Michael Dougan
Journal for ImmunoTherapy of Cancer 
2020;8:e000958  (24 June 2020)
Research

Calcium-sensing receptor autoantibody-mediated hypoparathyroidism associated with immune checkpoint inhibitor therapy: diagnosis and long-term follow-up

Ramona Dadu, Theresa E Rodgers, Van A Trinh, Elizabeth Helen Kemp, Trisha D Cubb, Sapna Patel, Julie M Simon, Elizabeth M Burton, Hussein Tawbi
Journal for ImmunoTherapy of Cancer 
2020;8:e000687  (24 June 2020)
Case Report

Involvement of the M-CSF/IL-34/CSF-1R pathway in malignant pleural mesothelioma

Thibaut Blondy, Sènan Mickael d'Almeida, Tina Briolay, Julie Tabiasco, Clément Meiller, Anne-Laure Chéné, Laurent Cellerin, Sophie Deshayes, Yves Delneste, Jean-François Fonteneau, Nicolas Boisgerault, Jaafar Bennouna, Marc Grégoire, Didier Jean, Christophe Blanquart
Journal for ImmunoTherapy of Cancer 
2020;8:e000182  (24 June 2020)
Research

IL-6 promotes PD-L1 expression in monocytes and macrophages by decreasing protein tyrosine phosphatase receptor type O expression in human hepatocellular carcinoma

Wenjie Zhang, Yang Liu, Zhongyi Yan, Hui Yang, Wei Sun, Yongliang Yao, Yun Chen, Runqiu Jiang
Journal for ImmunoTherapy of Cancer 
2020;8:e000285  (24 June 2020)
Research

Bivalent therapeutic vaccine against HPV16/18 genotypes consisting of a fusion protein between the extra domain A from human fibronectin and HPV16/18 E7 viral antigens

Laura Arribillaga, Iciar Echeverria, Viriginia Belsue, Timothy Gomez, Teresa Lozano, Noelia Casares, Lorea Villanueva, Sonia Domingos-Pereira, Pedro J Romero, Denise Nardelli-Haefliger, Sandra Hervás-Stubbs, Pablo Sarobe, María Josefa Rodriguez, José L Carrascosa, Thomas Zürcher, Juan José Lasarte
Journal for ImmunoTherapy of Cancer 
2020;8:e000704  (24 June 2020)
Research

Lung metastases share common immune features regardless of primary tumor origin

Sandra García-Mulero, M Henar Alonso, Julián Pardo, Cristina Santos, Xavier Sanjuan, Ramón Salazar, Victor Moreno, Josep María Piulats, Rebeca Sanz-Pamplona
Journal for ImmunoTherapy of Cancer 
2020;8:e000491  (25 June 2020)
Research

Safety and immunogenicity of novel 5T4 viral vectored vaccination regimens in early stage prostate cancer: a phase I clinical trial

Federica Cappuccini, Richard Bryant, Emily Pollock, Lucy Carter, Clare Verrill, Julianne Hollidge, Ian Poulton, Megan Baker, Celia Mitton, Andrea Baines, Armin Meier, Guenter Schmidt, Richard Harrop, Andrew Protheroe, Ruth MacPherson, Steven Kennish, Susan Morgan, Selena Vigano, Pedro J Romero, Thomas Evans, James Catto, Freddie Hamdy, Adrian V S Hill, Irina Redchenko
Journal for ImmunoTherapy of Cancer 
2020;8:e000928  (25 June 2020)
Research

Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes

Alejandro Meraz-Muñoz, Eitan Amir, Pamela Ng, Carmen Avila-Casado, Claire Ragobar, Christopher Chan, Joseph Kim, Ron Wald, Abhijat Kitchlu
Journal for ImmunoTherapy of Cancer 
2020;8:e000467  (29 June 2020)
Research

Tim-3 finds its place in the cancer immunotherapy landscape

Nandini Acharya, Catherine Sabatos-Peyton, Ana Carrizosa Anderson
Journal for ImmunoTherapy of Cancer 
2020;8:e000911  (29 June 2020)
Review

CD8+CD57+ T cells exhibit distinct features in human non-small cell lung cancer

Bing HuangRong LiuPeiliang WangZhiwei YuanJianjian YangHui XiongNi ZhangQi HuangXiangning FuWei SunLequn Li
Journal for ImmunoTherapy of Cancer 
2020;8:e000639  (30 June 2020)
Research

Development and validation of a genomic mutation signature to predict response to PD-1 inhibitors in non-squamous NSCLC: a multicohort study

Xue BaiDe-Hua WuSi-Cong MaJian WangXin-Ran TangShuai KangQiang John FuChuan-Hui CaoHe-San LuoYu-Han ChenHong-Bo ZhuHong-Hong YanYi-Long WuZhong-Yi Dong
Journal for ImmunoTherapy of Cancer 
2020;8:e000381  (30 June 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.