JITC Digest September 2020

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Inside this Issue:

Letter from the Editor

Dear JITC Readers,pedro-romero_1__1_.jpg

It is a pleasure to welcome you to this edition of the JITC digest. A new academic year is getting underway for many of our readers, and regardless of the “new normal” imposed by COVID-19, the journal continues to publish groundbreaking research from across the immunotherapy field.
 
The articles spotlighted in this month’s digest exemplify how the immunotherapy field excels at bringing a new perspective to processes or therapies that might be considered familiar—thus advancing our discipline in novel and important new directions.
 
John C. Flickinger Jr., and colleagues creatively overcome the obstacle inherent in many cancer vaccine approaches of pre-existing host immunity to the adenoviral backbone by engineering a new chimeric vector.
 
By taking a new look at a familiar cytokine, Tal Kan et al provide evidence that IL-31 may induce anti-tumor immunity in breast cancer.
 
New immune response biomarkers that could help identify patients with melanoma who may benefit from combination radiotherapy and CTLA-4 blockade are described by Celine Boutros and colleagues. Additionally, evidence for safety and efficacy with retreatment with anti-PD-L1 therapy after discontinuation for reasons other than toxicity or progression is provided by Siddharth Sheth et al.
 
Although the results were negative for a first-in-human trial for a first-in-class, orally administered, selective dual inhibitor of IDO1 and TDO2, reported by Aung Naing and colleagues, the findings could set the stage for future studies of rational combinations of therapies targeting tryptophan metabolism and other immunotherapy agents.
 
Finally, a first-of-its-kind study by Pedro Barata et al demonstrates the feasibility of using a commercially available cell-free DNA assay to identify patients with advanced prostate cancer and microsatellite instability-high tumors who may benefit from pembrolizumab.
 
To further your reading this month, be sure to browse JITC’s Reading List, with an intriguing selection of papers drawn from the viral immunology world, selected by Dr. Howard Kaufman.
 
Best regards,

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


JITC Editor Picks

Chimeric Ad5.F35 vector evades anti-adenovirus serotype 5 neutralization opposing GUCY2C-targeted antitumor immunity

John C Flickinger Jr, Jagmohan Singh, Robert Carlson, Elinor Leong, Trevor R Baybutt, Joshua Barton, Ellen Caparosa, Amanda Pattison, Jeffrey A Rappaport, Jamin Roh, Tingting Zhan, Babar Bashir, Scott A Waldman, Adam E SnookJournal for ImmunoTherapy of Cancer 2020;8:e001046 (20 August 2020)
Guideline

Summary:

The adenovirus serotype 5 (Ad5) vector is commonly used as a backbone for cancer vaccines, however, pre-existing antibodies to Ad5 are present in more than 70% of the world’s population due to previous exposure via natural infection. To expand the population who may benefit from Ad5-based vaccine strategies, John C Flickinger Jr et al generated a chimeric vector with the fiber of Ad5 replaced by that of Ad35 (Ad5.F35) and carrying the gastrointestinal cancer antigen guanylyl cyclase C (GUCY2C). No toxicity signals were observed with the Ad5.F35-based vaccine in mouse models, and long-lasting T cell responses were observed against the GUCY2C antigen after vaccination. In challenge models, both Ad5- and Ad5.F35-based vaccines produced GUCY2C-specific CD8+ T cells of comparable avidity and both had identical efficacy in reducing tumor burden, slowing disease progression, and promoting survival. The numbers of antigen-specific CD8+ T cells elicited by vaccination were reduced to a lesser degree with pre-exposure to Ad5 in animals receiving the Ad5.F35-based vaccine compared to vaccination with the parental vector. In sera from patients with colorectal cancer enrolled in the Ad5-GUCY2C-PADRE phase I trial (which evaluated an Ad5-based vaccine), Ad5.F35-specific neutralizing antibody titers were substantially lower than Ad5-specific titers, with only 50% of patients possessing low anti-Ad5 titers compared to 90% with low anti-Ad5.F35 titers.

IL-31 induces antitumor immunity in breast carcinoma

Tal Kan, Erik Feldman, Michael Timaner, Ziv Raviv, Shai Shen-Orr, Ami Aronheim, Yuval Shaked
Journal for ImmunoTherapy of Cancer 2020;8:e001010  (24 August 2020)

Research

Summary:

Interleukin (IL)-31, a proinflammatory cytokine from the IL-6 family, acts as an antiangiogenic agent and emerging data from mouse models lacking the IL-31 receptor hint at a role in regulation of type 2 inflammation. To characterize a potentially immunomodulatory role for the cytokine in breast cancer, Tal Kan and colleagues implanted mice with two different IL-31-expressing carcinoma cell lines: PyMT (a model for Luminal B breast carcinoma) and EMT6 (a model for triple negative breast cancer). Tumor growth rates were reduced for both subtypes, although the decrease was more pronounced for the PyMT model. Intratumoral granzyme B levels and CD8+ central memory T cell counts were elevated in the IL-31-expressing PyMT tumors, while the levels of CD4+CD25+ T cells and CD4+ effector memory T cells were reduced. Furthermore, fewer immunosuppressive M2 macrophages myeloid-derived suppressor cells (MDSCs) were present within tumors expressing IL-31, while proinflammatory M1 macrophage populations were increased. Although IL-31 had no apparent effect on the activation state or proliferation rate of isolated splenic CD8+ T cells in vitro, in co-culture experiments where MDSCs were present, treatment with the cytokine significantly increased the frequency of CD8+ T cells with central memory phenotype. In cultures of whole splenocytes, the addition of IL-31 resulted in inhibition of MDSC cell motility. IL-31-treated M2 macrophages secreted higher levels of factors associated with recruitment, activation, and survival of lymphocytes, as well as higher levels of Pentraxin 3, which inhibits metastasis. In mice harboring PyMT tumors and treated with a recombinant IL-31 bound to an IgG backbone, tumor growth was inhibited and significantly lower levels of intratumoral CD4+CD25+ T cells, tumor-associated macrophages and MDSCs were observed compared to in control IgG-treated mice.

Dose escalation phase 1 study of radiotherapy in combination with anti-cytotoxic-T-lymphocyte-associated antigen 4 monoclonal antibody ipilimumab in patients with metastatic melanoma

Celine Boutros, Nathalie Chaput-Gras, Emilie Lanoy, Alicia Larive, Christine Mateus, Emilie Routier, Roger Sun, Yun Gan Tao, Christophe Massard, Rastilav Bahleda, Dominique Schwob, Nathalie Ibrahim, Rita Maria Khoury Abboud, Caroline Caramella, Andrea Lancia, Lydie Cassard, Severine Roy, J -C Soria, Caroline Robert, Eric Deutsch
Journal for ImmunoTherapy of Cancer 2020;8:e000627 (20 August 2020)
Research

Summary:

Preclinical models have demonstrated synergy between radiotherapy and anti-CTLA-4 checkpoint blockade. In the Mel-Ipi-Rx phase I study, Celine Boutros et al determined the maximum tolerated dose (MTD) and safety profile of radiotherapy combined with ipilimumab in checkpoint inhibitor naïve patients with metastatic melanoma. Using a 3+3 dose escalation design, 19 patients were treated with 9, 15, 18 and 24 Gy doses of radiotherapy combined with ipilimumab at 10 mg/kg every 3 weeks for four doses. Nine patients experienced Grade 3 adverse events, with the most common being colitis and hepatitis. A total of four patients experienced dose-limiting toxicities that led to permanent discontinuation of ipilimumab. The MTD for radiotherapy was determined to be 9 Gy. The objective response rate was 31%, with 2 complete responses, 3 partial responses and 7 cases of stable disease, for a clinical benefit rate of 75% at week 24. Response of non-irradiated lesions was numerically more representative of patient outcomes as compared to responses in irradiated lesions, but the number of patients was too low for statistical testing. Analysis of immune cells revealed significant increases in CD4+ T effector memory ICOS+CD4+ T cells at week 6. High fold changes in CD8+ T cell counts from baseline to week 4 was significantly associated with progression-free, but not overall survival. The findings point toward immune response biomarkers that could identify a subset of patients that may benefit from combination radio- and immunotherapy.

Durvalumab activity in previously treated patients who stopped durvalumab without disease progression

Siddharth Sheth, Chen Gao, Nancy Mueller, Natasha Angra, Ashok Gupta, Caroline Germa, Pablo Martinez, Jean-Charles Soria
Journal for ImmunoTherapy of Cancer 2020;8:e000650 (26 August 2020)

Research

Summary:

Select few studies have evaluated reinitiation of ipilimumab, pembrolizumab, or nivolumab in previously-treated patients, but data are sparse on potential clinical benefit with retreatment with anti-PD-L1 therapies. Siddharth Sheth and colleagues evaluated safety and efficacy of durvalumab retreatment in patients with advanced solid tumors who were taken off therapy at 1 year per study protocol and subsequently experienced disease progression. Among the 168 patients who completed 1 year of initial durvalumab therapy, 70 underwent retreatment, with 14 tumor types represented, most commonly non-small cell lung cancer, microsatellite instability (MSI-H) cancers, urothelial carcinoma, squamous cell carcinoma of the head and neck, and hepatocellular carcinoma. Patients with an objective response to initial durvalumab therapy experienced a longer time off treatment until disease progression compared with those without, but objective responses during initial treatment were not associated with objective responses or longer times to disease progression during retreatment. Median time to response was generally shorter with initial treatment compared with retreatment, but the median duration of responses were similar. The disease control rates and 12-month progression-free survival rates with retreatment were roughly half of those with initial therapy. Response rates, disease control rates, and median duration of responses were generally greater in patients with high PD-L1 expression than those with low or negative expression. No new safety signals were observed during retreatment. The findings support retreatment of patients who stop anti-PD-L1 therapy for reasons other than progression or toxicity.

Preclinical investigations and a first-in-human phase I trial of M4112, the first dual inhibitor of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase 2, in patients with advanced solid tumors

Aung Naing, Joseph P Eder, Sarina A Piha-Paul, Claude Gimmi, Elizabeth Hussey, Sen Zhang, Vera Hildebrand, Vinayak Hosagrahara, Christina Habermehl, Jacques Moisan, Kyriakos P Papadopoulos
Journal for ImmunoTherapy of Cancer 2020;8:e000870 (24 August 2020)

Research

Summary:

Overexpression of IDO1 and TDO1—the enzymes that catalyze the first, rate-limiting step in the conversion of tryptophan to the immunosuppressive metabolite kynurenine—is associated with poor prognosis in several types of cancer. Aung Naing and colleagues report pre-clinical and first-in human phase I data on the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy, of M4112, a first-in-class, orally administered, selective dual inhibitor of IDO1 and TDO2. In multiple mouse models of IDO1-expressing tumors, dose-dependent reductions in the kynurenine:tryptophan ratio were observed in the liver and plasma of mice after M4112 administration. For the phase I trial, 15 patients received M4112 at five dose levels. Inhibition of IDO1 in ex vivo stimulated blood was seen within four hours after M4112 across all doses tested. However, despite initial increases in plasma tryptophan levels after dosing, kynurenine levels returned to baseline levels by day 15 of cycle 1, leading to study discontinuation due to insufficient pharmacodynamic effect. The best overall response was stable disease in nine patients. One dose-limiting toxicity occurred: a case of grade 3 allergic dermatitis. Neither the maximum tolerated dose nor the recommended phase II dose were established. Although dual inhibition of IDO1 and TDO2 may be insufficient to provoke antitumor responses alone, the findings lay the groundwork for future studies investigating rational combinations with other immuno-oncology agents. In this regard, it is worth noting a recent report identifying interleukin-4-induced-1 (IL4I1) as a major aryl hydrocarbon receptor (AHR)-activating enzyme that is not inhibited by IDO1 inhibitors. IL4I1-mediated tryptophan catabolism, promoted AHR-driven cancer cell motility and suppressed adaptive immunity (Sadik A et alCell 2020, https://doi.org/10.1016/j.cell.2020.07.038).

Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA

Pedro Barata, Neeraj Agarwal, Roberto Nussenzveig, Benjamin Gerendash, Ellen Jaeger, Whitley Hatton, Elisa Ledet, Brian Lewis, Jodi Layton, Hani Babiker, Alan Bryce, Rohan Garje, Cy Stein, Lesli Kiedrowski, Philip Saylor, Oliver Sartor
Journal for ImmunoTherapy of Cancer 2020;8:e001065 (11 August 2020)

Short Report

Summary:

Checkpoint inhibitor therapy has demonstrated limited benefit to date for unselected metastatic castration-resistant prostate cancer (mCRPC). Based on the tissue-agnostic approval for pembrolizumab for the treatment of microsatellite instability high (MSI-H) tumors, Pedro Barata and colleagues used the commercially available next-generation sequencing assay Guardant360 to identify patients with mCRPC eligible for therapy based on analysis of cell-free DNA (cfDNA). Testing was performed for 460 patients with advanced prostate cancer across eight academic centers. Among the 14 patients with MSI-H metastatic prostate cancer, 9 were treated with pembrolizumab. Declines in prostate-specific antigen (PSA) of greater than 50% from baseline were observed in four patients after pembrolizumab therapy, with three achieving greater than 99% reductions. At data cut-off, four patients were still on therapy, while four patients discontinued pembrolizumab due to progressive disease and one due to SARS-CoV-2 infection. MSI-H was also detected in tumor tissue NGS for all three patients with available tissue, however, no germline genomic alterations were found in the two patients who underwent separate germline testing. The report supports the use of liquid biopsy to identify metastatic prostate cancer patients with MSI-H tumors for potential treatment with pembrolizumab.

Impact of body composition on outcomes from anti-PD1 +/- anti-CTLA-4 treatment in melanoma

Arissa C Young, Henry T Quach, Haocan Song, Elizabeth J Davis, Javid J Moslehi, Fei Ye, Grant R Williams, Douglas B Johnson
Journal for ImmunoTherapy of Cancer 
2020;8:e000821 (2 August 2020)
Research

Reintroduction of immune-checkpoint inhibitors after immune-related meningitis: a case series of melanoma patients

Stefania Cuzzubbo, Pauline Tetu, Sarah Guegan, Renata Ursu, Catherine Belin, Lila Sirven Villaros, Julie Mazoyer, Coralie Lheure, Celeste Lebbe, Barouyr Baroudjian, Antoine F Carpentier
Journal for ImmunoTherapy of Cancer 
2020;8:e001034 (2 August 2020)
Short Report

Future role for adoptive T-cell therapy in checkpoint inhibitor-resistant metastatic melanoma

Troels Holz Borch, Rikke Andersen, Eva Ellebaek, Özcan Met, Marco Donia, Inge Marie Svane
Journal for ImmunoTherapy of Cancer 
2020;8:e000668 (2 August 2020)
Short Report

PD-1 does not mark tumor-infiltrating CD8+ T cell dysfunction in human gastric cancer

Yang Shen, Yongsheng Teng, Yipin Lv, Yongliang Zhao, Yuan Qiu, Weisan Chen, Lina Wang, Ying Wang, Fangyuan Mao, Ping Cheng, Daiyuan Ma, Yuan Zhuang, Quanming Zou, Liusheng Peng
Journal for ImmunoTherapy of Cancer 2020;8:e000422  (4 August 2020)
Research

An open-label, phase II multicohort study of an oral hypomethylating agent CC-486 and durvalumab in advanced solid tumors

Kirsty Taylor, Helen Loo Yau, Ankur Chakravarthy, Ben Wang, Shu Yi Shen, Ilias Ettayebi, Charles A Ishak, Philippe L Bedard, Albiruni Abdul Razak, Aaron R Hansen, Anna Spreafico, Dave Cescon, Marcus O Butler, Amit M Oza, Stephanie Lheureux, Neda Stjepanovic, Brendan Van As, Sarah Boross-Harmer, Lisa Wang, Trevor J Pugh, Pamela S Ohashi, Lillian L Siu, Daniel D De Carvalho
Journal for ImmunoTherapy of Cancer 2020;8:e000883  (4 August 2020)
Research

Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up

Bo-Kyeong Jung, Hae Young Ko, Hyunji Kang, JinWoo Hong, Hyo Min Ahn, Youjin Na, Hyeongi Kim, Jin Su Kim, Chae-Ok Yun
Journal for ImmunoTherapy of Cancer 2020;8:e000848  (4 August 2020)
Research

Outcomes to first-line pembrolizumab in patients with PD-L1-high (>/=50%) non–small cell lung cancer and a poor performance status

Joao V Alessi, Biagio Ricciuti, Elizabeth Jiménez-Aguilar, Fangxin Hong, Zihan Wei, Mizuki Nishino, Andrew J Plodkowski, Peter Sawan, Jia Luo, Hira Rizvi, Brett W Carter, John V Heymach, Mehmet Altan, Matthew Hellmann, Mark Awad
Journal for ImmunoTherapy of Cancer 2020;8:e001007  (4  August 2020)
Short Report

Is there a link between very early changes of primary and secondary lymphoid organs in 18F-FDG-PET/MRI and treatment response to checkpoint inhibitor therapy?

Ferdinand Seith, Andrea Forschner, Benjamin Weide, Brigitte Gückel, Martin Schwartz, Johannes Schwenck, Ahmed E Othman, Matthias Fenchel, Claus Garbe, Konstantin Nikolaou, Nina Schwenzer, Christian la Fougère, Christina Pfannenberg
Journal for ImmunoTherapy of Cancer 
2020;8:e000656 (4 August 2020)
Short Report

Rationalized inhibition of mixed lineage kinase 3 and CD70 enhances life span and antitumor efficacy of CD8+ T cells

Sandeep Kumar, Sunil Kumar Singh, Navin Viswakarma, Gautam Sondarva, Rakesh Sathish Nair, Periannan Sethupathi, Matthew Dorman, Subhash C Sinha, Kent Hoskins, Gregory Thatcher, Basabi Rana, Ajay Rana
Journal for ImmunoTherapy of Cancer 2020;8:e000494  (5 August 2020)
Research

Combining BRAF inhibition with oncolytic herpes simplex virus enhances the immune-mediated antitumor therapy of BRAF-mutant thyroid cancer

Eva Crespo-Rodriguez, Katharina Bergerhoff, Galabina Bozhanova, Shane Foo, Emmanuel C Patin, Harriet Whittock, Richard Buus, Syed Haider, Gareth Muirhead, Khin Thway, Kate Newbold, Robert S Coffin, Richard G Vile, Dae Kim, Martin McLaughlin, Alan A Melcher, Kevin J Harrington, Malin PedersenJournal for ImmunoTherapy of Cancer 2020;8:e000698  (5 August 2020)
Research

A recombinant oncolytic Newcastle virus expressing MIP-3alpha promotes systemic antitumor immunity

Feng-Ying Huang, Jin-Yan Wang, Shu-Zhen Dai, Ying-Ying Lin, Yan Sun, Liming Zhang, Zhuoxuan Lu, Rong Cao, Guang-Hong Tan
Journal for ImmunoTherapy of Cancer 2020;8:e000330  (5 August 2020)
Research

Efficacy of immunotherapy in lung cancer with co-occurring mutations in NOTCH and homologous repair genes

Feng-Ying Huang, Jin-Yan Wang, Shu-Zhen Dai, Ying-Ying Lin, Yan Sun, Liming Zhang, Zhuoxuan Lu, Rong Cao, Guang-Hong Tan
Journal for ImmunoTherapy of Cancer 2020;8:e000946  (5 August 2020)
Short Report

Genetic associations of T cell cancer immune response-related genes with T cell phenotypes and clinical outcomes of early-stage lung cancer

Qinchaung Wang, Jianchun Gu, Linbo Wang, David W Chang, Yuanqing Ye, Maosheng Huang, Jack A Roth, Xifeng Wu
Journal for ImmunoTherapy of Cancer 2020;8:e000336  (6 August 2020)
Research

CD163+ cytokine-producing cDC2 stimulate intratumoral type 1 T cell responses in HPV16-induced oropharyngeal cancer

Saskia J Santegoets, Chantal L Duurland, Ekaterina J Jordanova, Vanessa J van Ham, Ilina Ehsan, Nikki M Loof, Vipin Narang, Charles A Dutertre, Florent Ginhoux, Sylvia L van Egmond, Marij J P Welters, Sjoerd H van der Burg
Journal for ImmunoTherapy of Cancer 
2020;8:e001053  (7 August 2020)
Research

Antagonistic anti-LILRB1 monoclonal antibody regulates antitumor functions of natural killer cells

Heyu Chen, Yuanzhi Chen, Mi Deng, Samuel John, Xun Gui, Ankit Kansagra, Weina Chen, Jaehyup Kim, Cheryl Lewis, Guojin Wu, Jingjing Xie, Lingbo Zhang, Ryan Huang, Xiaoye Liu, Hisashi Arase, Yang Huang, Hai Yu, Wenxin Luo, Ningshao Xia, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang
Journal for ImmunoTherapy of Cancer 
2020;8:e000515 (7 August 2020)
Research

Discovery and validation of surface N-glycoproteins in MM cell lines and patient samples uncovers immunotherapy targets

Robyn A A Oldham, Mary L Faber, Theodore R Keppel, Amanda R Buchberger, Matthew Waas, Parameswaran Hari, Rebekah L Gundry, Jeffrey A Medin
Journal for ImmunoTherapy of Cancer 
2020;8:e000915 (7 August 2020)
Research

IL-6 regulates CCR5 expression and immunosuppressive capacity of MDSC in murine melanoma

Rebekka Weber, Zeno Riester, Laura Hüser, Carsten Sticht, Alina Siebenmorgen, Christopher Groth, Xiaoying Hu, Peter Altevogt, Jochen S Utikal, Viktor Umansky
Journal for ImmunoTherapy of Cancer 
2020;8:e000949 (11 August 2020)
Research

Outcomes and biomarker analyses among patients with COVID-19 treated with interleukin 6 (IL-6) receptor antagonist sarilumab at a single institution in Italy

Vincenzo Montesarchio, Roberto Parrella, Chiara Iommelli, Antonella Bianco, Elio Manzillo, Fiorentino Fraganza, Cristiana Palumbo, Gaetano Rea, Patrizia Murino, Rosanna De Rosa, Luigi Atripaldi, Maurizio D’Abbraccio, Marcello Curvietto, Domenico Mallardo, Egidio Celentano, Antonio Maria Grimaldi, Marco Palla, Claudia Trojaniello, Maria Grazia Vitale, Samuel Lewis Million-Weaver, Paolo Antonio Ascierto
Journal for ImmunoTherapy of Cancer
 
2020;8:e001089  (11 August 2020)
Case Report

Oxazaphosphorines combined with immune checkpoint blockers: dose-dependent tuning between immune and cytotoxic effects

Julia Delahousse, Charles Skarbek, Mélanie Desbois, Jean-Luc Perfettini, Nathalie Chaput, Angelo Paci
Journal for ImmunoTherapy of Cancer 2020;8:e000916  (11 August 2020)
Research

Efficient elimination of primary B-ALL cells in vitro and in vivo using a novel 4-1BB-based CAR targeting a membrane-distal CD22 epitope

Talia Velasco-Hernandez, Samanta Romina Zanetti, Heleia Roca-Ho, Francisco Gutierrez-Aguera, Paolo Petazzi, Diego Sánchez-Martínez, Oscar Molina, Matteo Libero Baroni, Jose Luis Fuster, Paola Ballerini, Clara Bueno, Narcis Fernandez-Fuentes, Pablo Engel, Pablo Menendez
Journal for ImmunoTherapy of Cancer 2020;8:e000896 (11 August 2020)
Research

Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma

M Hope Robinson, Juan Vasquez, Akhilesh Kaushal, Tobey J MacDonald, José E Velázquez Vega, Matthew Schniederjan, Kavita Dhodapkar
Journal for ImmunoTherapy of Cancer 2020;8:e001066  (11 August 2020)
Research

Differential quantities of immune checkpoint-expressing CD8 T cells in soft tissue sarcoma subtypes

Yarne Klaver, Maud Rijnders, Astrid Oostvogels, Rebecca Wijers, Marcel Smid, Dirk Grünhagen, Cornelis Verhoef, Stefan Sleijfer, Cor Lamers, Reno Debets
Journal for ImmunoTherapy of Cancer 2020;8:e000271  (13 August 2020)
Research

Safety and efficacy of CAR-T cell targeting BCMA in patients with multiple myeloma coinfected with chronic hepatitis B virus

Lu Han, Jian Zhou, Keshu Zhou, Xinghu Zhu, Lingdi Zhao, Baijun Fang, Qingsong Yin, Xudong Wei, Hu Zhou, Linlin Li, Bengling Xu, Jishuai Zhang, Yongping Song, Quanli Gao
Journal for ImmunoTherapy of Cancer 
2020;8:e000927 (13 August 2020)
Research

Tumor copy-number alterations predict response to immune-checkpoint-blockade in gastrointestinal cancer

Zhihao Lu, Huan Chen, Shuang Li, Jifang Gong, Jian Li, Jianling Zou, Lihong Wu, Jianing Yu, Wenbo Han, Huaibo Sun, Xi Jiao, Xiaotian Zhang, Zhi Peng, Ming Lu, Zhenghang Wang, Henghui Zhang, Lin Shen
Journal for ImmunoTherapy of Cancer 
2020;8:e000374 (13 August 2020)
Research

Enhanced immunotherapeutic profile of oncolytic virus-based cancer vaccination using cyclophosphamide preconditioning

Jonathan G Pol, Matthew J Atherton, Kyle B Stephenson, Byram W Bridle, Samuel T Workenhe, Natasha Kazdhan, AJ Robert McGray, Yonghong Wan, Guido Kroemer, Brian D Lichty
Journal for ImmunoTherapy of Cancer 2020;8:e000981 (13 August 2020)
Short Report

Prediction of immune checkpoint inhibition with immune oncology-related gene expression in gastrointestinal cancer using a machine learning classifier

Zhihao Lu, Huan Chen, Xi Jiao, Wei Zhou, Wenbo Han, Shuang Li, Chang Liu, Jifang Gong, Jian Li, Xiaotian Zhang, Xicheng Wang, Zhi Peng, Changsong Qi, Zhenghang Wang, Yanyan Li, Jie Li, Yan Li, Malcolm Brock, Henghui Zhang, Lin Shen
Journal for ImmunoTherapy of Cancer 
2020;8:e000631 (13 August 2020)
Short Report

Rapid tumor vaccine using Toll-like receptor-activated ovarian cancer ascites monocytes

Sarah F Adams, Alizée J Grimm, Cheryl L-L Chiang, Ananda Mookerjee, Dallas Flies, Stephanie Jean, Georgia A McCann, Justine Michaux, HuiSong Pak, Florian Huber, Christopher Neal, Denarda Dangaj, Michal Bassani-Sternberg, Sylvie Rusakiewicz, Andrea Facciabene, George Coukos, Phyllis A Gimotty, Lana E Kandalaft
Journal for ImmunoTherapy of Cancer 
2020;8:e000875 (16 August 2020)
Research

Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer

Zhaopei Liu, Quan Zhou, Zewei Wang, Hongyu Zhang, Han Zeng, Qiuren Huang, Yifan Chen, Wenbin Jiang, Zhiyuan Lin, Yang Qu, Ying Xiong, Qi Bai, Yu Xia, Yiwei Wang, Li Liu, Yu Zhu, Le Xu, Bo Dai, Jianming Guo, Jiajun Wang, Yuan Chang, Weijuan Zhang
Journal for ImmunoTherapy of Cancer 
2020;8:e000978 (16 August 2020)
Research

Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles

Jacob J Orme, Elizabeth Ann L Enninga, Fabrice Lucien-Matteoni, Heather Dale, Edwin Burgstaler, Susan M Harrington, Matthew K Ball, Aaron S Mansfield, Sean S Park, Mathew S Block, Svetomir N Markovic, Yiyi Yan, Haidong Dong, Roxana S Dronca, Jeffrey L Winters
Journal for ImmunoTherapy of Cancer 2020;8:e001113  (17 August 2020)
Research

Remodeling tumor immune microenvironment (TIME) for glioma therapy using multi-targeting liposomal codelivery

Zening Zheng, Jiaxin Zhang, Jizong Jiang, Yang He, Wenyuan Zhang, Xiaopeng Mo, Xuejia Kang, Qin Xu, Bing Wang, Yongzhuo Huang
Journal for ImmunoTherapy of Cancer 2020;8:e000207  (17 August 2020)
Research

Genetic ablation of adipocyte PD-L1 reduces tumor growth but accentuates obesity-associated inflammation

Bogang Wu, Huai-Chin Chiang, Xiujie Sun, Bin Yuan, Payal Mitra, Yanfen Hu, Tyler J Curiel, Rong Li
Journal for ImmunoTherapy of Cancer 2020;8:e000964  (17 August 2020)
Short Report

Short-course radiotherapy promotes pro-inflammatory macrophages via extracellular vesicles in human rectal cancer

Victoria Stary, Brigitte Wolf, Daniela Unterleuthner, Julia List, Merjem Talic, Johannes Längle, Andrea Beer, Johanna Strobl, Georg Stary, Helmut Dolznig, Michael Bergmann, MD
Journal for ImmunoTherapy of Cancer 2020;8:e001009  (18 August 2020)
Research

Novel platform leveraging electronic medical record (EMR) to triage patients admitted with high-grade immune-related adverse events (irAEs) to the immune-toxicity (ITOX) service

Osama Abu-Shawer, Prabhsimranjot Singh, Eric Yenulevich, Amanda Brito, Jian Ni, Raja-Elie E Abdulnour, Shilpa Grover, Michael Manos, Peter Bowling, Nicole R LeBoeuf, Patrick Ott, F Stephen Hodi, Joseph Jacobson, Osama Rahma
Journal for ImmunoTherapy of Cancer 
2020;8:e000992 (18 August 2020)
Research

Combination of thermally ablative focused ultrasound with gemcitabine controls breast cancer via adaptive immunity

Natasha D Sheybani, Alexandra R Witter, Eric A Thim, Hideo Yagita, Timothy N J Bullock, Richard J Price
Journal for ImmunoTherapy of Cancer 
2020;8:e001008 (20 August 2020)
Research

An immune evasion mechanism with IgG4 playing an essential role in cancer and implication for immunotherapy

Hui Wang, Qian Xu, Chanyuan Zhao, Ziqi Zhu, Xiaoqing Zhu, Junjie Zhou, Shuming Zhang, Tiqun Yang, Biying Zhang, Jun Li, Meiling Yan, Renming Liu, Changchun Ma, Yan Quan, Yongqu Zhang, Weifeng Zhang, Yiqun Geng, Chuangzhen Chen, Shaobin Chen, Ditian Liu, Yuping Chen, Dongping Tian, Min Su, Xueling Chen, Jiang Gu
Journal for ImmunoTherapy of Cancer 
2020;8:e000661 (20 August 2020)
Research

M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer

Michal Hensler, Lenka Kasikova, Karel Fiser, Jana Rakova, Petr Skapa, Jan Laco, Tereza Lanickova, Ladislav Pecen, Iva Truxova, Sarka Vosahlikova, Irena Moserova, Ivan Praznovec, Vit Drochytek, Martina Rehackova, Tomas Brtnicky, Lukas Rob, Vladimir Benes, Jelena Pistolic, Ludek Sojka, Ales Ryska, Catherine Sautes-Fridman, Wolf Herve Fridman, Lorenzo Galluzzi, Radek Spisek, Jitka Fucikova
Journal for ImmunoTherapy of Cancer 
2020;8:e000979 (20 August 2020)
Research

Anti-tumor effects of NK cells and anti-PD-L1 antibody with antibody-dependent cellular cytotoxicity in PD-L1-positive cancer cell lines

Ji-Eun Park, Seong-Eun Kim, Bhumsuk Keam, Ha-Ram Park, Soyeon Kim, Miso Kim, Tae Min Kim, Junsang Doh, Dong-Wan Kim, Dae Seog Heo
Journal for ImmunoTherapy of Cancer 
2020;8:e000873 (23 August 2020)
Research

HITM-SURE: Hepatic immunotherapy for metastases phase Ib anti-CEA CAR-T study utilizing pressure enabled drug delivery

Steven C Katz, Ashley E Moody, Prajna Guha, John C Hardaway, Ethan Prince, Jason LaPorte, Mirela Stancu, Jill E Slansky, Kimberly R Jordan, Richard D Schulick, Robert Knight, Abdul Saied, Vincent Armenio, Richard P Junghans
Journal for ImmunoTherapy of Cancer 
2020;8:e001097 (24 August 2020)
Case Report

The Great Debate at ‘Immunotherapy Bridge’, Naples, December 5, 2019

Paolo A Ascierto, Carlo Bifulco, Jerome Galon, Claus Garbe, Samir N Khleif, Jennifer McQuade, Kunle Odunsi, Hideho Okada, Chrystal M Paulos, Sergio A Quezada, Hussein A Tawbi, John Timmerman, Giorgio Trinchieri, Lisa H Butterfield, Igor Puzanov
Journal for ImmunoTherapy of Cancer 
2020;8:e000921 (24 August 2020)
Meeting Report

Rationalizing the pathway to personalized neoadjuvant immunotherapy: the Lombard Street Approach

Judith M Versluis, Daniela S Thommen, Christian U Blank
Journal for ImmunoTherapy of Cancer 
2020;8:e001352 (24 August 2020)
Review

Mirage or long-awaited oasis: reinvigorating T-cell responses in pancreatic cancer

Michael Brandon Ware, Bassel F El-Rayes, Gregory B Lesinski
Journal for ImmunoTherapy of Cancer 
2020;8:e001110 (25 August 2020)
Review

Guillain-Barré syndrome after adoptive cell therapy with tumor-infiltrating lymphocytes

Angela Orcurto, Andreas Hottinger, Benita Wolf, Blanca Navarro Rodrigo, Maria Ochoa de Olza, Aymeric Auger, Thierry Kuntzer, Denis Comte, Virginie Zimmer, Philippe Gannon, Lana Kandalaft, Olivier Michielin, Stefan Zimmermann, Alexandre Harari, Lionel Trueb, George Coukos
Journal for ImmunoTherapy of Cancer 
2020;8:e001155 (26 August 2020)
Case Report

Immunohistochemical scoring of CD38 in the tumor microenvironment predicts responsiveness to anti-PD-1/PD-L1 immunotherapy in hepatocellular carcinoma

Harry Ho Man Ng, Ren Yuan Lee, Siting Goh, Isabel Shu Ying Tay, Xinru Lim, Bernett Lee, Valerie Chew, Huihua Li, Benedict Tan, Sherlly Lim, Jeffrey Chun Tatt Lim, Bijin Au, Josh Jie Hua Loh, Sahil Saraf, John Edward Connolly, Tracy Loh, Wei Qiang Leow, Joycelyn Jie Xin Lee, Han Chong Toh, Fabio Malavasi, Ser Yee Lee, Pierce Chow, Evan W Newell, Su Pin Choo, David Tai, Joe Yeong, Tony Kiat Hon Lim
Journal for ImmunoTherapy of Cancer 
2020;8:e000987 (26 August 2020)
Research

Overcoming resistance to STING agonist therapy to incite durable protective antitumor immunity

Henrique Lemos, Rong Ou, Caroline McCardle, Yijun Lin, Jessica Calver, Jack Minett, Ahmed Chadli, Lei Huang, Andrew L Mellor
Journal for ImmunoTherapy of Cancer 
2020;8:e001182 (26 August 2020)
Research

Combination therapy with T cell engager and PD-L1 blockade enhances the antitumor potency of T cells as predicted by a QSP model

Huilin Ma, Hanwen Wang, Richard J Sové, Jun Wang, Craig Giragossian, Aleksander S Popel
Journal for ImmunoTherapy of Cancer 
2020;8:e001141 (27 August 2020)
Research

Brain metastasis PD-L1 and CD8 expression is dependent on primary tumor type and its PD-L1 and CD8 status

Florian CamyGeorgia KarpathiouJean Marc DumollardNicolas MagneJean Luc PerrotFrancois VassalTiphanie PicotMousa MobarkiFabien ForestFrancois CasteilloSirine HathroubiMarios FroudarakisMichel Peoc'hJournal for ImmunoTherapy of Cancer 2020;8:e000597 (27 August 2020)
Research

Antigen processing and presentation in cancer immunotherapy

Maxwell Y Lee, Jun W Jeon, Cem Sievers, Clint T Allen
Journal for ImmunoTherapy of Cancer 
2020;8:e001111 (27 August 2020)
Review

Somatic POLE exonuclease domain mutations elicit enhanced intratumoral immune responses in stage II colorectal cancer

Shaobo Mo, Xiaoji Ma, Yaqi Li, Long Zhang, Ting Hou, Han Han-Zhang, Juanjuan Qian, Sanjun Cai, Dan Huang, Junjie Peng
Journal for ImmunoTherapy of Cancer 
2020;8:e000881 (27 August 2020)
Short Report

Immune-related pneumonitis associated with immune checkpoint inhibitors in lung cancer: a network meta-analysis

Xinru Chen, Zhonghan Zhang, Xue Hou, Yaxiong Zhang, Ting Zhou, Jiaqing Liu, Zhihuan Lin, Wenfeng Fang, Yunpeng Yang, Yuxiang Ma, Yan Huang, Hongyun Zhao, Li Zhang
Journal for ImmunoTherapy of Cancer 
2020;8:e001170 (30 August 2020)
Research

Risk of HBV reactivation in patients with immune checkpoint inhibitor-treated unresectable hepatocellular carcinoma

Pei-Chang Lee, Yee Chao, Ming-Huang Chen, Keng-Hsin Lan, I-Cheng Lee, Ming-Chih Hou, Yi-Hsiang Huang
Journal for ImmunoTherapy of Cancer 
2020;8:e001072 (18 August 2020)
Research

IFN-gamma treatment protocol for MHC-Ilo/PD-L1+ pancreatic tumor cells selectively restores their TAP-mediated presentation competence and CD8 T-cell priming potential

Katja Stifter, Jana Krieger, Leonie Ruths, Johann Gout, Medhanie Mulaw, Andre Lechel, Alexander Kleger, Thomas Seufferlein, Martin Wagner, Reinhold Schirmbeck
Journal for ImmunoTherapy of Cancer 
2020;8:e000692 (31 August 2020)
Research

Post-registration experience of nivolumab in advanced hepatocellular carcinoma: an international study

Petros Fessas, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, ChiehJu Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Francesca Benevento, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Marron, David J Pinato
Journal for ImmunoTherapy of Cancer 
2020;8:e001033 (31 August 2020)
Research

Bone marrow MSC from pediatric patients with B-ALL highly immunosuppress T-cell responses but do not compromise CD19-CAR T-cell activity

Samanta Romina Zanetti, Paola Alejandra Romecin, Meritxell Vinyoles, Manel Juan, José Luis Fuster, Mireia Cámos, Sergi Querol, Mario Delgado, Pablo Menendez
Journal for ImmunoTherapy of Cancer 
2020;8:e001419 (31 August 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.