JITC Digest January 2021

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Inside this Issue:

Letter from the Editor

Dear JITC Readers,pedro-romero_1__1_.jpg

Happy new year and welcome to the first JITC digest of 2021. Even against the backdrop of the global COVID-19 pandemic, last year was a banner year for immuno-oncology, with immunotherapy becoming the standard of care in more and more disease settings. I look ahead to 2021 with optimism that the immunotherapy field will continue apace—providing lifesaving options for patients with cancer and advancing our understanding of the basic immunological mechanisms of tumor control.
 
During the month of December, four new papers from the Society for Immunotherapy of Cancer (SITC) were published in JITC, including the clinical practice guideline on immune effector cell-related adverse events, which will be of great value to the hematology and oncology communities. The journal is proud to support the society’s goal of scientific exchange by publishing these excellent peer-reviewed papers among the top-tier research that appears in JITC.
 
The original research articles highlighted in this month’s digest all provide new insight into one of the most challenging questions in our field: Why does checkpoint inhibition induce deep and durable responses in some, but not all, tumors?
 
Joshua R Veatch and colleagues develop an elegant enrichment and deep-sequencing strategy to show that neoantigen-responsive T cells were associated with tumor control in one patient with melanoma—shining light on a relatively minor contribution of self-antigen reactive T cells.
 
Expanding our understanding of potential immune checkpoints beyond PD-1 in virus-associated solid tumors, Isobel Okoye et al identify upregulation of the TIM-3 ligand galectin-9 as a marker of functional exhaustion and impaired T cell and natural killer NK cell responses.
 
The exhaustion phenotypes of T cells from primary and metastatic sites in ovarian cancers are clearly delineated by Galam Leem and colleagues, identifying 4-1BB costimulation as a potential means to reinvigorate defective immune responses in this setting.
 
Finally, in a provocative rebuke of the so-called “obesity paradox,” Shannon K Boi et al show that high body mass index is associated with worse outcomes with PD-1 inhibition for renal cell carcinoma in the real-world setting, and use mouse models to provide mechanistic insight into a role for IL-1 beta in diminished responses to therapy.
 
With best wishes for the coming year,

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


JITC Editor Picks

Mobilization of pre-existing polyclonal T cells specific to neoantigens but not self-antigens during treatment of a patient with melanoma with bempegaldesleukin and nivolumab

Joshua R Veatch, Naina Singhi, Brenda Jesernig, Kelly G Paulson, Jonathan Zalevsky, Ernesto Iaccucci, Scott S Tykodi, Stanley R Riddell
Journal for ImmunoTherapy of Cancer 2020;8:e001591 (9 December 2020)
Research

Summary:

Tumor control after checkpoint blockade depends upon T cells specific for either neoantigens or self-antigens, and the relative contribution of each population is not known. Using a two-step enrichment process to expand peptide-stimulated T cells and select for antigen-specific clones, Joshua R Veatch and colleagues demonstrate the pre-treatment presence and on-treatment expansion of neoantigen-recognizing T cells in a patient with BRAFV600E-mutated melanoma who achieved disease control with bempegaldesleukin and nivolumab. Whole-exome sequencing revealed 279 single-nucleotide variants as possible neoantigens in addition to the BRAFV600E mutation, and 45 candidates were evaluated for T cell responses. Both CD8+ and CD4+ T cell responses were seen against mutated SLC39A14, and T cell-specific responses to additional variants were identified as well. Deep sequencing revealed a total of 54 neoantigen-specific TCRV-beta clonotypes, 32 of which were detectable in the tumor pre-treatment, making up 0.71% of the population. In unstimulated pre-treatment peripheral blood mononuclear cells, four of the clones were detected, accounting for a mere 0.005% of TCRV-beta sequences. In the first 5 days after treatment, neoantigen-specific clones expanded five-fold in the peripheral blood and then contracted to pre-treatment levels by 13 months. In the tumor, neoantigen-specific TCRV-beta sequences expanded by roughly 30%. By contrast, clonotypes specific for self-antigens (gp100, MAGE A3, TRP2, and tyrosinase) did not expand in the peripheral blood nor localize to the tumor. The results demonstrate a sophisticated enrichment method for identifying neoantigen-specific T cells, and suggest a likely role for these antigen specificities in tumor control.

Galectin-9 expression defines exhausted T cells and impaired cytotoxic NK cells in patients with virus-associated solid tumors

Isobel Okoye, Lai Xu, Melika Motamedi, Pallavi Parashar, John W Walker, Shokrollah Elahi
Journal for ImmunoTherapy of Cancer 2020;8:e001849  (12 December 2020)

Research

Summary:

Upregulation of the TIM-3 ligand galectin-9 (Gal-9) has been linked to impaired T cell effector function in patients with HIV, but its effects in the context of cancer are unknown. Isobel Okoye et al profiled Gal-9 expression in peripheral blood and tumor-infiltrating T cells in samples from 40 patients with virus-associated solid tumors who were treated with oral valproate and avelumab in the non-randomized phase II LATENT trial. Significant upregulation of surface Gal-9 was seen on both CD4+ and CD8+ T cells in peripheral blood before the initiation of treatment. Overexpression of Gal-9 correlated with impaired effector function, including reduced IL-2, interferon gamma, and tumor necrosis factor alpha secretion across T cell subsets, and attenuated granzyme B and perforin production. Co-expression of Gal-9 with PD-1 and TIGIT was seen on CD4+ T cells and associated with reduced cytokine production. Patients with treatment-responsive disease had lower levels of Gal-9 mRNA in the tumor microenvironment, and the group with progressive disease had elevated levels of Gal-9-expressing CD8+ T cells in the peripheral blood. No differences in the patterns of Gal-9 expression were seen in natural killer (NK) cells after therapy. Intriguingly, Gal-9-expressing NK cells showed impaired granzyme B and perforin production with enhanced interferon gamma expression. In vitro, Gal-9 displayed dispersed cytosolic localization in resting T cells, and was recruited to the surface upon stimulation. The findings reveal Gal-9 as a marker of functional exhaustion in T cells and NK cells in patients with virus-associated solid tumors, opening the door for further studies to explore if preventing upregulation of the lectin on T cells may enhance checkpoint blockade efficacy.

4-1BB co-stimulation further enhances anti-PD-1-mediated reinvigoration of exhausted CD39+ CD8 T cells from primary and metastatic sites of epithelial ovarian cancers

Galam Leem, Junsik Park, Minwoo Jeon, Eui-Soon Kim, Sang Wun Kim, Yong Jae Lee, Seong Jin Choi, Baekgyu Choi, Seongyeol Park, Young Seok Ju, Inkyung Jung, Sunghoon Kim, Eui-Cheol Shin, Jung Yun Lee, Su-Hyung Park
Journal for ImmunoTherapy of Cancer 2020;8:e001650 (16 December 2020)
Research

Summary:

Ovarian cancer is poorly responsive to checkpoint blockade. To investigate the exhaustion and activation phenotypes of T cells in primary tumor and metastatic site samples from 65 patients with ovarian cancer, Galam Leem et al performed immunophenotyping via multicolor flow cytometry, RNA sequencing, and ex vivo functional restoration assays. The frequencies of PD-1+, CTLA-4+ and Tim-3+ cells were significantly higher in CD8+ tumor-infiltrating lymphocytes (TILs) compared to CD8+ cells in peripheral blood. No differences in PD-1 or CD69 expression were seen between tumor-specific CD8+ TILs and tumor-unrelated virus-specific CD8+ T cells. Significantly, higher frequencies of CD39 and CD103 expression were seen in tumor-specific CD8+ TILs compared to in the virus-specific population. Subdividing the CD39+ TILs into three categories based on PD-1 expression, the frequencies of CTLA-4+ and Tim-3+ cells were significantly elevated in the subpopulation with the highest levels of PD-1. High-PD-1 expressing cells also showed elevated Eomes and low T-bet, indicative of terminal exhaustion. Notably, a substantial proportion of these terminally exhausted (PD-1high CD39+ CD8+ TILs) also expressed 4-1BB. The 4-1BB-positive population displayed phenotypes indicative of higher degrees of proliferation (Ki-67) and exhaustion status (Tcf-1, Eomes and T-bet). No significant differences in exhaustion and proliferation status were seen between primary tumors and metastatic sites. Ex vivo, 4-1BB costimulation with an agonistic antibody combined with PD-1 blockade enhanced proliferative capacity and cytokine production in exhausted TILs. A total of 520 genes were differentially expressed between the 4-1BB-positive and -negative CD39+ TILs, and a signature comprised of 177 of these genes was correlated with better survival outcomes in an ovarian cancer cohort from The Cancer Genome Atlas. The study is the first to analyze distinct characteristics of tumor-specific exhausted CD8+ TILs, identifying a 4-1BB-expressing subpopulation that may represent a potential target for reinvigoration to enhance the efficacy of checkpoint inhibition in ovarian cancer.

Obesity diminishes response to PD-1-based immunotherapies in renal cancer

Shannon K Boi, Rachael M Orlandella, Justin Tyler Gibson, William James Turbitt, Gal Wald, Lewis Thomas, Claire Buchta Rosean, Katlyn E Norris, Megan Bing, Laura Bertrand, Brett P Gross, Amani Makkouk, Dmytro Starenki, Kristine I Farag, Robert E Sorge, James A Brown, Jennifer Gordetsky, Hesham Yasin, Rohan Garje, Lakshminarayanan Nandagopal, George J Weiner, David M Lubaroff, Rebecca C Arend, Peng Li, Yousef Zakharia, Eddy Yang, Aliasger K Salem, Kenneth Nepple, Tatiana T Marquez-Lago, Lyse A Norian
Journal for ImmunoTherapy of Cancer 2020;8:e000725 (22 December 2020)

Research

Summary:

Multiple retrospective analyses have suggested that response rates to checkpoint inhibition in clinical trials positively correlate with body mass index (BMI) in some tumor types—the so called “obesity paradox” in cancer. In one of the first analyses of the impact of obesity on checkpoint inhibitor efficacy in the standard of care setting for renal cell carcinoma (RCC), Shannon K Boi and colleagues show that patients with BMI greater than the World Health Organization cutpoint of 30 kg/m2 had a median 6.5-month reduction in progression-free survival and a 12-month reduction in overall survival. Analyses of treatment-naïve CD8+ tumor-infiltrating lymphocytes (TILs) from patients with RCC showed that although activation statuses were not altered, obesity was associated with significantly reduced PD-1+CD8+ and PD-1highCD8+ populations. The altered TIL composition before treatment was recapitulated in orthotopic mouse models of RCC against a well-characterized background of diet-induced obesity. Furthermore, effector function, specifically interferon gamma secretion, was compromised in PD-1highCD8+ TILs in obese mice. The efficacy of a combination immunotherapy regimen comprised of adenovirus encoding murine TRAIL (AdTR) coadministered with the toll-like receptor 9 agonist CpG (AdTR/CpG) at day 7 post-tumor challenge plus anti-PD-1 was compromised in obese mice. Transcriptomic analyses and hierarchical clustering, however, revealed that tumors that responded to treatment clustered together regardless of obesity status—tumor control was characterized by robust expansion of intratumoral PD-1intCD8+ T cells that produced interferon gamma, tumor necrosis factor alpha and perforin. No obvious defects in T cell priming were observed in obese mice, yet significantly higher numbers of myeloid-derived suppressor cells (MDSCs) were found compared to the frequencies in lean hosts. Treatment-naïve obese mice had increased intratumoral concentrations of GM-CSF, IL-1-beta, CXCL1 and CCL2. Neutralization of IL-1 beta in addition to the combination immunotherapy regimen almost doubled the response rate in obese mice. The study comprehensively establishes mechanism whereby obesity may be detrimental to checkpoint blockade outcomes in RCC, motivating further examination of the “obesity paradox” in other settings.

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events

Marcela V Maus, Sara Alexander, Michael R Bishop, Jennifer N Brudno, Colleen Callahan, Marco L Davila, Claudia Diamonte, Jorg Dietrich, Julie C Fitzgerald, Matthew J Frigault, Terry J Fry, Jennifer L Holter-Chakrabarty, Krishna V Komanduri, Daniel W Lee, Frederick L Locke, Shannon L Maude, Philip L McCarthy, Elena Mead, Sattva S Neelapu, Tomas G Neilan, Bianca D Santomasso, Elizabeth J Shpall, David T Teachey, Cameron J Turtle, Tom Whitehead, Stephan A Grupp
Journal for ImmunoTherapy of Cancer 2020;8:e001511 (16 December 2020)

Research

Summary:

Chimeric antigen receptor (CAR) T cell therapies may offer durable responses in patients with relapsed hematologic malignancies that formerly carried a dismal prognosis, but as “living drugs” these treatments are associated with a unique spectrum of toxicities that may be challenging to manage. To offer practical guidance for oncologists and improve outcomes for patients, the Society for Immunotherapy of Cancer convened a panel of experts in the cell therapy field to develop evidence- and consensus-based recommendations on the optimal management of clinically significant toxicities with CAR T cell therapy, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cardiotoxicity, and other important concerns such as infectious disease prophylaxis and quality of life. As one of the first clinical practice guidelines specifically devoted to toxicity management for cell therapies, and developed by a panel that included perspectives from subspecialties, nursing, and patient advocacy, this will be an invaluable resource for the hematology and oncology communities, especially as the landscape of this revolutionary class of immunotherapy continues to expand.

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lymphoma

Sattva S Neelapu, Sherry Adkins, Stephen M Ansell, Joshua Brody, Mitchell S Cairo, Jonathan W Friedberg, Justin P Kline, Ronald Levy, David L Porter, Koen van Besien, Michael Werner, Michael R Bishop
Journal for ImmunoTherapy of Cancer 
2020;8:e001235 (24 December 2020)
Guideline

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events

Marcela V Maus, Sara Alexander, Michael R Bishop, Jennifer N Brudno, Colleen Callahan, Marco L Davila, Claudia Diamonte, Jorg Dietrich, Julie C Fitzgerald, Matthew J Frigault, Terry J Fry, Jennifer L Holter-Chakrabarty, Krishna V Komanduri, Daniel W Lee, Frederick L Locke, Shannon L Maude, Philip L McCarthy, Elena Mead, Sattva S Neelapu, Tomas G Neilan, Bianca D Santomasso, Elizabeth J Shpall, David T Teachey, Cameron J Turtle, Tom Whitehead, Stephan A Grupp
Journal for ImmunoTherapy of Cancer 
2020;8:e001511 (16 December 2020)
Guideline

Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume II—practical challenges

Alessandra Cesano, Michael A Cannarile, Sacha Gnjatic, Bruno Gomes, Justin Guinney, Vaios Karanikas, Mohan Karkada, John M Kirkwood, Beatrix Kotlan, Giuseppe V Masucci, Els Meeusen, Anne Monette, Aung Naing, Vésteinn Thorsson, Nicholas Tschernia, Ena Wang, Daniel K Wells, Timothy L Wyant, Sergio Rutella
Journal for ImmunoTherapy of Cancer 
2020;8:e001472 (15 December 2020)
Resource

SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery

Siwen Hu-Lieskovan, Srabani Bhaumik, Kavita Dhodapkar, Jean-Charles J B Grivel, Sumati Gupta, Brent A Hanks, Sylvia Janetzki, Thomas O Kleen, Yoshinobu Koguchi, Amanda W Lund, Cristina Maccalli, Yolanda D Mahnke, Ruslan D Novosiadly, Senthamil R Selvan, Tasha Sims, Yingdong Zhao, Holden T Maecker
Journal for ImmunoTherapy of Cancer 2020;8:e000705  (2 December 2020)
Resource

Comprehensive analysis of cutaneous and uveal melanoma liver metastases

Esmee P Hoefsmit, Elisa A Rozeman, Trieu My Van, Petros Dimitriadis, Oscar Krijgsman, Jordan W Conway, Ines Pires da Silva, Jacqueline E van der Wal, Steven L C Ketelaars, Kaspar Bresser, Annegien Broeks, Ron M Kerkhoven, Jason W Reeves, Sarah Warren, Pia Kvistborg, Richard A Scolyer, Ellen W Kapiteijn, Daniel S Peeper, Georgina V Long, Ton N M Schumacher, Christian U Blank
Journal for ImmunoTherapy of Cancer 
2020;8:e001501 (1 December 2020)
Research

Mitochondrial Lon-induced mtDNA leakage contributes to PD-L1–mediated immunoescape via STING-IFN signaling and extracellular vesicles

An Ning Cheng, Li-Chun Cheng, Cheng-Liang Kuo, Yu Kang Lo, Han-Yu Chou, Chung-Hsing Chen, Yi-Hao Wang, Tsung-Hsien Chuang, Shih-Jung Cheng, Alan Yueh-Luen Lee
Journal for ImmunoTherapy of Cancer 
2020;8:e001372 (2 December 2020)
Research

Combining inhibition of galectin-3 with and before a therapeutic vaccination is critical for the prostate-tumor-free outcome

Carolina Tiraboschi, Lucas Gentilini, Carla Velazquez, Enrique Corapi, Felipe Martín Jaworski, José Daniel Garcia Garcia, Yorfer Rondón, Anne Chauchereau, Diego José Laderach, Daniel Compagno
Journal for ImmunoTherapy of Cancer 
2020;8:e001535 (8 December 2020)
Research

Adenoviral vaccines promote protective tissue-resident memory T cell populations against cancer

Esmé TI van der Gracht, Mark JA Schoonderwoerd, Suzanne van Duikeren, Ayse N Yilmaz, Felix M Behr, Julia M Colston, Lian N Lee, Hideo Yagita, Klaas PJM van Gisbergen, Lukas JAC Hawinkels, Frits Koning, Paul Klenerman, Ramon Arens
Journal for ImmunoTherapy of Cancer 2020;8:e001133  (8 December 2020)
Research

Intensified immunosuppressive therapy in patients with immune checkpoint inhibitor-induced myocarditis

Jennifer Cautela, Sarah Zeriouh, Melanie Gaubert, Laurent Bonello, Marc Laine, Michael Peyrol, Franck Paganelli, Nathalie Lalevee, Fabrice Barlesi, Franck Thuny
Journal for ImmunoTherapy of Cancer 2020;8:e001887  (8 December 2020)
Research

Role of immunotherapy in Ewing sarcoma

Erin Morales, Michael Olson, Fiorella Iglesias, Saurabh Dahiya, Tim Luetkens, Djordje Atanackovic
Journal for ImmunoTherapy of Cancer 2020;8:e000653  (8 December 2020)
Review

A20 regulates the therapeutic effect of anti-PD-1 immunotherapy in melanoma

Weinan Guo, Jinyuan Ma, Sen Guo, Huina Wang, Sijia Wang, Qiong Shi, Lin Liu, Tao Zhao, Fengfan Yang, Shuyang Chen, Jianru Chen, Jianhong Zhao, Chen Yu, Xiuli Yi, Yuqi Yang, Jingjing Ma, Qingrong Ni, Guannan Zhu, Tianwen Gao, Chunying Li
Journal for ImmunoTherapy of Cancer 2020;8:e001866  (9 December 2020)
Research

Increased rates of immunosuppressive treatment and hospitalization after checkpoint inhibitor therapy in cancer patients with autoimmune disease

David Andrew Bender, Samuel P Heilbroner, Tony J C Wang, Catherine A Shu, Brigham Hyde, Catherine Spina, Simon K Cheng
Journal for ImmunoTherapy of Cancer 
2020;8:e001627 (10 December 2020)
Research

Management of immune checkpoint therapy for patients with cancer in the face of COVID-19

Chen Shen, Qianru Li, Yongchang Wei, Yuting Li, Jun Li, Juan Tao
Journal for ImmunoTherapy of Cancer 2020;8:e001593  (10 December 2020)
Commentary

Systemic and intravesical adoptive cell therapy of tumor-reactive T cells can decrease bladder tumor growth in vivo

Brittany L Bunch, Jennifer Morse, Sarah Asby, Jamie Blauvelt, Ahmet M Aydin, Patrick Innamarato, Ali Hajiran, Matthew Beatty, Michael Poch, Shari Pilon-Thomas
Journal for ImmunoTherapy of Cancer 2020;8:e001673  (10 November 2020)
Research

EPHA mutation as a predictor of immunotherapeutic efficacy in lung adenocarcinoma

Hua Bai, Jianchun Duan, Chengcheng Li, Wenzhuan Xie, Wenfeng Fang, Yu Xu, Guoqiang Wang, Rui Wan, Jing Sun, Jiachen Xu, Xin Wang, Kailun Fei, Zhengyi Zhao, Shangli Cai, Li Zhang, Jie Wang, Zhijie Wang
Journal for ImmunoTherapy of Cancer 2020;8:e001315  (10 December 2020)
Research

Strategies for improving the management of immune-related adverse events

Aung Naing, Joud Hajjar, James L Gulley, Michael B Atkins, Gennaro Ciliberto, Funda Meric-Bernstam, Patrick Hwu
Journal for ImmunoTherapy of Cancer 2020;8:e001754  (12 December 2020)
Guideline

Complement controls the immune synapse and tumors control complement

Alan Herbert
Journal for ImmunoTherapy of Cancer 2020;8:e001712  (15 December 2020)
Hypothesis

In vivo therapeutic effects of affinity-improved-TCR engineered T-cells on HBV-related hepatocellular carcinoma

Qi Liu, Ye Tian, Yanyan Li, Wei Zhang, Wenxuan Cai, Yaju Liu, Yuefei Ren, Zhaoduan Liang, Peipei Zhou, Yajing Zhang, Yifeng Bao, Yi Li
Journal for ImmunoTherapy of Cancer 
2020;8:e001748  (15 December 2020)
Research

Bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with human papillomavirus-associated malignancies

Julius Strauss, Margaret E Gatti-Mays, Byoung Chul Cho, Andrew Hill, Sébastien Salas, Edward McClay, Jason M Redman, Houssein A Sater, Renee N Donahue, Caroline Jochems, Elizabeth Lamping, Andrea Burmeister, Jennifer L Marté, Lisa M Cordes, Marijo Bilusic, Fatima Karzai, Laureen S Ojalvo, Genevieve Jehl, P Alexander Rolfe, Christian S Hinrichs, Ravi A Madan, Jeffrey Schlom, James L Gulley
Journal for ImmunoTherapy of Cancer 
2020;8:e001395 (15 December 2020)
Research

Immune-mediated ototoxicity associated with immune checkpoint inhibitors in patients with melanoma

Samuel Rosner, Yuri Agrawal, Daniel Q Sun, Nafi Aygun, Megan D Schollenberger, Evan Lipson, Jarushka Naidoo
Journal for ImmunoTherapy of Cancer 
2020;8:e001675 (16 December 2020)
Case Report

Antibody profiling of patients with prostate cancer reveals differences in antibody signatures among disease stages

Hemanth K Potluri, Tun Lee Ng, Michael A Newton, Jin Zhang, Christopher A Maher, Peter S Nelson, Douglas G McNeel
Journal for ImmunoTherapy of Cancer 
2020;8:e001510 (16 December 2020)
Research

Phagocytic function of tumor-associated macrophages as a key determinant of tumor progression control: a review

Marc Lecoultre, Valérie Dutoit, Paul R Walker
Journal for ImmunoTherapy of Cancer
 
2020;8:e001408  (17 December 2020)
Review

Initiation of immunotherapy with activated natural killer cells and anti-GD2 antibody dinutuximab prior to resection of primary neuroblastoma prolongs survival in mice

Michael John Zobel, Abigail K Zamora, Hong-wei Wu, Jianping Sun, Danny Lascano, Jemily Malvar, Larry Wang, Michael A Sheard, Robert C Seeger, Eugene S Kim
Journal for ImmunoTherapy of Cancer 2020;8:e001560  (18 December 2020)
Research

Landscape of natural killer cell activity in head and neck squamous cell carcinoma

Andrew J Charap, Tomohiro Enokida, Rachel Brody, John Sfakianos, Brett Miles, Nina Bhardwaj, Amir Horowitz
Journal for ImmunoTherapy of Cancer 2020;8:e001523 (21 December 2020)
Review

Safety of immune checkpoint inhibitor rechallenge after discontinuation for grade >=2 immune-related adverse events in patients with cancer

Marion Allouchery, Thomas Lombard, Mickael Martin, Franck Rouby, Marion Sassier, Celia Bertin, Marina Atzenhoffer, Ghada Miremont-Salame, Marie-Christine Perault-Pochat, Mathieu Puyade
Journal for ImmunoTherapy of Cancer 2020;8:e001622  (21 December 2020)
Research

Durvalumab and tremelimumab with or without stereotactic body radiation therapy in relapsed small cell lung cancer: a randomized phase II study

Suchita Pakkala, Kristin Higgins, Zhengjia Chen, Gabriel Sica, Conor Steuer, Chao Zhang, Guojing Zhang, Shuhua Wang, Mohammad S Hossain, Bassel Nazha, Tyler Beardslee, Fadlo R Khuri, Walter Curran, Sagar Lonial, Edmund K Waller, Suresh Ramalingam, Taofeek K Owonikoko
Journal for ImmunoTherapy of Cancer 2020;8:e001302  (21 December 2020)
Research

Domain binding and isotype dictate the activity of anti-human OX40 antibodies

Jordana Griffiths, Khiyam Hussain, Hannah L Smith, Theodore Sanders, Kerry L Cox, Monika Semmrich, Linda Mårtensson, Jinny Kim, Tatyana Inzhelevskaya, Chris A Penfold, Alison L Tutt, C Ian Mockridge, HT Claude Chan, Vikki English, Ruth F French, Ingrid Teige, Aymen Al-Shamkhani, Martin J Glennie, Bjorn L Frendeus, Jane E Willoughby, Mark S Cragg
Journal for ImmunoTherapy of Cancer 
2020;8:e001557 (21 December 2020)
Research

Blood-based kinase activity profiling: a potential predictor of response to immune checkpoint inhibition in metastatic cancer

Daan P Hurkmans, Els M E Verdegaal, Sabrina A Hogan, Rik de Wijn, Lies Hovestad, Dianne M A van den Heuvel, Rob Ruijtenbeek, Marij J P Welters, Mandy van Brakel, Edwin A Basak, Herbert M Pinedo, Cor H J Lamers, Harmen J G van de Werken, John P Groten, Reno Debets, Mitchell P Levesque, Reinhard Dummer, Ellen Kapiteijn, Ron H J Mathijssen, Joachim G J V Aerts, Sjoerd H van der Burg
Journal for ImmunoTherapy of Cancer 
2020;8:e001607 (22 December 2020)
Research

Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study

Nazanin Majd, Steven G Waguespack, Filip Janku, Siqing Fu, Marta Penas-Prado, Mingxuan Xu, Anas Alshawa, Carlos Kamiya-Matsuoka, Shaan M Raza, Ian E McCutcheon, Aung Naing
Journal for ImmunoTherapy of Cancer 2020;8:e001532 (22 December 2020)
Research

Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma

Motoki Nakamura, Kotaro Nagase, Maki Yoshimitsu, Tetsuya Magara, Yuka Nojiri, Hiroshi Kato, Tadahiro Kobayashi, Yukiko Teramoto, Masahito Yasuda, Hidefumi Wada, Toshiyuki Ozawa, Yukie Umemori, Dai Ogata, Akimichi Morita
Journal for ImmunoTherapy of Cancer 
2020;8:e001679 (23 December 2020)
Research

Serum CD73 is a prognostic factor in patients with metastatic melanoma and is associated with response to anti-PD-1 therapy

Roberta Turiello, Mariaelena Capone, Diana Giannarelli, Elva Morretta, Maria Chiara Monti, Gabriele Madonna, Domenico Mallardo, Lucia Festino, Rosa Azzaro, Mitchell P Levesque, Laurence Imhof, Benjamin Weide, Teresa Amaral, Marc Chevrier, Antje Sucker, Piotr Rutkowski, Dirk Schadendorf, Celeste Lebbe, Jason John Luke, Kilian Wistuba-Hamprecht, Reinhard Dummer, Aldo Pinto, Silvana Morello, Paolo A Ascierto
Journal for ImmunoTherapy of Cancer 
2020;8:e001689 (23 December 2020)
Research

KEYNOTE-022 part 3: a randomized, double-blind, phase 2 study of pembrolizumab, dabrafenib, and trametinib in BRAF-mutant melanoma

Pier Francesco Ferrucci, Anna Maria Di Giacomo, Michele Del Vecchio, Victoria Atkinson, Henrik Schmidt, Jacob Schachter, Paola Queirolo, Georgina V Long, Rosalie Stephens, Inge Marie Svane, Michal Lotem, Mahmoud Abu-Amna, Eduard Gasal, Razi Ghori, Scott J Diede, Elizabeth S Croydon, Antoni Ribas, Paolo Antonio Ascierto
Journal for ImmunoTherapy of Cancer 
2020;8:e001806 (24 December 2020)
Research

SITC Members Receive 50 Percent Submission Discount in 2021

*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 2021.