JITC Digest June 2020

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Inside this Issue:

Letter from the Editor

Dear JITC Readers,pedro-romero_1__1_.jpg

Welcome to the latest edition of the JITC digest. As we move into the first months of the summer, cancer research programs are cautiously beginning to re-open in cities around the world while at the same time the streets are full of thousands of people protesting against racial injustice. In these tumultuous times, JITC is proud to add to the voices of all those across the globe in strong support of justice and equality, and against racism of any kind.
 
We hope that all our JITC readers are staying safe as shelter in place orders due to the COVID-19 pandemic slowly lift and we reaffirm our commitment to publishing the best of immunotherapy research through these tumultuous and uncharted times.
 
In this issue we are excited to share an excellent review, two perspectives from SITC and four original research articles, two of which describe important new biomarker approaches for predicting and monitoring therapeutic response and two of which develop strategies to enhance anti-tumor immunity.
 
John P Lynes and colleagues provide a timely update on strategies for the identification of predictive immunotherapy biomarkers in the highly heterogeneous central nervous system malignancy glioblastoma along with an overview of challenges for the field in central nervous system disease in, "Biomarkers for immunotherapy for treatment of glioblastoma."
 
In, "Endogenous TLR2 ligand embedded in the catalytic region of human cysteinyl-tRNA synthetase 1," Seongmin Cho et al. identify a unique TLR agonist embedded within the catalytic region of a human tRNA synthetase enzyme that significantly improved survival when administered with checkpoint inhibitors in mouse models without causing significant systemic toxicity.
 
Victor H Engelhard and colleagues developed, performed pre-clinical characterization and evaluated safety and immunogenicity of a novel immunotherapeutic vaccine comprising HLA-restricted phosphorylated peptides in, "MHC-restricted phosphopeptide antigens: preclinical validation and first-in-humans clinical trial in participants with high-risk melanoma."
 
On the biomarkers side, Thomas LaSalle and colleagues used a novel PET agent that non-invasively quantifies granzyme B release to measure immune cell activation in tumors during checkpoint inhibitor therapies. Additionally, in an impressive pan-tumor analysis, Jessica Roelands et al. demonstrate that cancer-specific oncogenic gene expression programs may modulate the predictive power of favorable intratumoral immune responses. Don't miss the papers, "Granzyme B PET imaging of immune-mediated tumor killing as a tool for understanding immunotherapy response" and "Oncogenic states dictate the prognostic and predictive connotations of intratumoral immune response."
 
JITC also is proud to publish two outstanding papers from SITC, "The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response" by Fernanda I Arnaldez et al. and "The Society for Immunotherapy of Cancer statement on best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) staining and validation" by Janis M Taube and colleagues. The former provides an overview of immune-modulatory therapies that may be of use for COVID-19 and the latter helps set standards to ensure outputs are robust and comparable across laboratories and platforms.
 
Finally, it is with a heavy heart that I share the passing of our colleague Beatrix Kotlan. Among her many amazing contributions to the immunotherapy field, Beatrix was a founding Associate Editor who served six years on the JITC editorial board. She was also a dedicated, enthusiastic reviewer and a tireless advocate for lower-income countries to have access to the tools and knowledge necessary to advance the field. Our thoughts are with her family.
 
Best regards,

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


JITC Editor Picks

The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response

Fernanda I Arnaldez, Steven J O'Day, Charles G Drake, Bernard A Fox, Bingqing Fu, Walter J Urba, Vincenzo Montesarchio, Jeffrey S Weber, Haiming Wei, Jon M Wigginton and Paolo Antonio Ascierto
Journal for ImmunoTherapy of Cancer 2020;8:e000930 (7 May 2020)
SITC Paper

Summary:

Initial experience from the COVID-19 outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. Drawing on extensive experience administering immune-modulating therapies, SITC identified potential alternatives to anti-IL-6 including modulation of IL-1, GM-CSF and TNF alpha as well as inhibition of JAK/STAT signaling.

The Society for Immunotherapy of Cancer statement on best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) staining and validation

Janis M Taube, Guray Akturk, Michael Angelo, Elizabeth L Engle, Sacha Gnjatic, Shirley Greenbaum, Noah F Greenwald, Cyrus V Hedvat, Travis J Hollmann, Jonathan Juco, Edwin R Parra, Marlon C Rebelatto, David L Rimm, Jaime Rodriguez-Canales, Kurt A Schalper, Edward C Stack, Cláudia S Ferreira, Konstanty Korski, Ana Lako, Scott J Rodig, Emanuel Schenck, Keith E Steele, Michael J Surace, Michael T Tetzlaff, Katharina von Loga, Ignacio I Wistuba and Carlo B Bifulco on behalf of the Society for Immunotherapy of Cancer (SITC) Pathology Task Force.
Journal for ImmunoTherapy of Cancer 2020;8:e000155  (15 May 2020)

SITC Paper

Summary:

Multiplex immunohistochemistry and immunofluorescence technologies are becoming standard tools for immunotherapy biomarker studies and are likely to enter routine clinical practice in the near future. In order to establish best practice guidelines for the optimization and validation of multiplex assays, SITC convened a task force of pathologists and laboratory leaders from academic centers as well as experts from pharmaceutical and diagnostic companies to discuss key considerations for ensuring that outputs are robust and comparable across institutions and platforms.

Endogenous TLR2 ligand embedded in the catalytic region of human cysteinyl-tRNA synthetase 1

Seongmin Cho, Sang Bum Kim, Youngjin Lee, Ee Chan Song, Uijoo Kim, Hyeong Yun Kim, Ji Hun Suh, Peter C Goughnour, YounHa Kim, Ina Yoon, Na Young Shin, Doyeun Kim, Il-Kyu Kim, Chang-Yuil Kang, Song Yee Jang, Myung Hee Kim and Sunghoon Kim
Journal for ImmunoTherapy of Cancer 2020;8:e000277 (26 May 2020)
Research

Summary:

The development of Toll-like receptor (TLR) ligands for immunotherapy has been hindered by rapid systemic toxicity with these agents. Seongmin Cho and colleagues identify an endogenous and novel TLR2/6 ligand embedded in the catalytic region of human cysteinyl-tRNA synthetase 1 (CARS1) that can act as an adjuvant to activate anti-tumor immune responses. Cultured human colon cancer cells secreted CARS1 under conditions of endoplasmic reticulum and inflammatory stress but not after treatment with growth factors and cytokines. Immunofluorescence and flow cytometry revealed preferential binding of CARS1 to macrophages and monocytes, but not B or T cells. A unique domain (UNE-C1) inserted into the catalytic region of CARS1 was necessary and sufficient for dendritic cell activation. Bone-marrow derived cells upregulated proinflammatory genes including il-6, nos2, il-12, cd40, cd80, and cd86 upon UNE-C1 treatment. In vivo, UNE-C1 increased antigen presentation on non-plasmacytoid dendritic cells. Immunization with OVA antigen combined with UNE-C1 produced specific anti-OVA antibodies and induced functional antigen-specific CD8+ T cells. In mouse models, a combination of vaccination with tumor antigen and UNE-C1 with anti-CTLA-4 treatment significantly improved survival. Importantly, UNE-C1 did not induce systemic toxicity in vivo, unlike known TLR agonists, which caused a significant release of inflammatory cytokines in treated mice. The findings suggest the UNE-C1 domain can be developed as an immunoadjuvant with checkpoint inhibitors or cancer antigens to boost antitumor immunity.

MHC-restricted phosphopeptide antigens: preclinical validation and first-in-humans clinical trial in participants with high-risk melanoma

Victor H Engelhard, Rebecca C Obeng, Kara L Cummings, Gina R Petroni, Angela L Ambakhutwala, Kimberly A Chianese-Bullock, Kelly T Smith, Amanda Lulu, Nikole Varhegyi, Mark E Smolkin, Paisley Myers, Keira E Mahoney, Jeffrey Shabanowitz, Nico Buettner, Emily H Hall, Kathleen Haden, Mark Cobbold, Donald F Hunt, Geoffrey Weiss, Elizabeth Gaughan and Craig L Slingluff, Jr
Journal for ImmunoTherapy of Cancer 2020;8:e000262 (7 May 2020)

Research

Summary:

Phosphorylated peptides presented by MHC molecules represent a new class of neoantigens that are promising targets for cancer vaccines. In prior studies, an HLA-A*0201-restricted phosphopeptide from insulin receptor substrate 2 (pIRS2) was identified as one such neoantigen. Here, Victor H Engelhard and colleagues identify and characterize a second phosphopeptide, from breast cancer antiestrogen resistance 3 (BCAR3), and evaluate safety and immunogenicity of a novel immunotherapeutic vaccine comprising phosphorylated peptides in a first-in-human trial. They show that a phosphopeptide of BCAR3 modified by substitution of V for L at residue 134 (for higher affinity for HLA-A*0201) called pBCAR3(V)126-134 induced antigen specific human T cells in vitro and was immunogenic in vivo in HLA-A2 transgenic mice. The phosphopeptide vaccine candidates were evaluated in an open-label, pilot, proof-of-concept study that enrolled 15 patients who had undergone surgical resection of stage II, III or IV melanoma to one of three arms: Arm A (3 patients) received pBCAR3126-134 only; Arm B (3 patients) received pIRS21097-1105 only; and Arm C (9 patients) was vaccinated with pBCAR3126-134 + pIRS21097-1105. All patients had grade 1 and 2 adverse events and all developed grade 2 vaccine injection site reactions. There were no treatment-related toxicities of grade 3 or greater. Overall 6 of 15 patients (40%) had a T cell response to either or both of the vaccine peptides with the majority of responses detected at a single time point, typically at weeks 3, 5 or 8. The estimated 4-year overall survival was 80% and the median disease-free survival was just over 1.0 year.

Granzyme B PET imaging of immune-mediated tumor killing as a tool for understanding immunotherapy response

Thomas LaSalle, Emily E Austin, Grant Rigney, Eric Wehrenberg-Klee, Sarah Nesti, Benjamin Larimer and Umar Mahmood
Journal for ImmunoTherapy of Cancer 2020;8:e000291 (26 May 2020)

Research

Summary:

Overall survival as an endpoint does not reflect the nuanced biology that may occur during an anti-tumor response. Using a novel PET agent that non-invasively quantifies granzyme B release in tumors, Thomas LaSalle and colleagues measured immune cell activation in tumors during checkpoint inhibitor therapies and identified cell types and cytokines that correlated with response to treatment. In murine MC38 tumors, which are mis-match repair deficient and immunologically "hot," early and robust granzyme B activity was detectable by PET, whereas the magnitude of the response was smaller in CT26 tumors, which are microsatellite stable. Across both tumors, granzyme B PET signal was negatively correlated with inactive T cells. Certain cytokines, such as tumor necrosis factor alpha, and macrophage inflammatory protein 1 beta (CCL4), were correlated with granzyme B response when found in both CT26 and MC38. However, these cytokines negatively corresponded with granzyme B in the lymph nodes, emphasizing the role tissue compartmentalization plays in the response. Intriguingly, eotaxin, which attracts eosinophils, was also correlated with response across both tumor types. Other cytokines, including IL-6, demonstrated distinct correlation patterns between MC38 and CT26 tumors and lymph nodes. The data provide proof of concept that granzyme B PET signal may help identify mechanisms of response to immunotherapy across a range of immunogenic tumor microenvironments

Oncogenic states dictate the prognostic and predictive connotations of intratumoral immune response

Jessica Roelands, Wouter Hendrickx, Gabriele Zoppoli, Raghvendra Mall, Mohamad Saad, Kyle Halliwill, Giuseppe Curigliano, Darawan Rinchai, Julie Decock, Lucia G Delogu, Tolga Turan, Josue Samayoa, Lotfi Chouchane, Alberto Ballestrero, Ena Wang, Pascal Finetti, Francois Bertucci, Lance D Miller, Jerome Galon, Francesco M Marincola, Peter J K Kuppen, Michele Ceccarelli, and Davide Bedognetti
Journal for ImmunoTherapy of Cancer 2020;8:e000617 (5 May 2020)

Research

Summary:

Pre-existing intratumoral anti-tumor T helper 1 (Th-1) immune responses have been linked to favorable outcomes with immunotherapy, but not all immunologically "hot" cancers respond to treatment. Building upon a previously defined gene expression signature called the Immunologic Constant of Rejection (ICR), Jessica Roelands and colleagues demonstrate that cancer-specific pathways modulate the prognostic power of favorable intratumoral immune responses. In a pan-tumor analysis of data from The Cancer Genome Atlas encompassing 31 different histologies from 9282 patients, high expression of the ICR signature was associated with significant survival benefit for some cancer types including breast invasive carcinoma, skin cutaneous melanoma, uterine corpus endometrial carcinoma, and sarcoma while being linked to significantly reduced OS in other cancer types such as uveal melanoma, low grade glioma, pancreatic adenocarcinoma and kidney renal clear cell carcinoma. ICR score was associated with significantly improved survival independent of mutation rate in cancers with increased proliferation and independent of proliferation in cancer with increased mutation rates. Notably, ICR scores were inversely correlated with expression of oncogenic pathway genes such as WNT-beta catenin signaling, AMPK signaling, telomerase extension, and Notch and Hedgehog signaling. Analysis of samples from melanoma patients treated with checkpoint inhibitors in the Van Allen melanoma dataset revealed association of high ICR scores pretreatment with survival only for samples with high proliferation scores. Conversely, ICR scores were only associated with survival in samples with low TGF beta expression. The results suggest that in tumors with high mutation burdens and/or high proliferation, ICR captures a true protective anti-tumor immune response, whereas in tumors dominated by cancer signaling ICR captures bystander or heavily suppressed immune infiltration with no protective effect.

Biomarkers for immunotherapy for treatment of glioblastoma

John P Lynes, Anthony K Nwankwo, Hannah P Sur, Victoria E Sanchez, Kwadwo A Sarpong, Oluwatobi I Ariyo, Gifty A Dominah and Edjah K Nduom
Journal for ImmunoTherapy of Cancer 2020;8:e000348 (30 May 2020)

Review

Summary:

Glioblastoma is known for exceptionally poor median survival and high recurrence rate with few treatment options. A highly immunosuppressive microenvironment along with profound intratumoral molecular heterogeneity pose particular challenges for the identification of actionable targets and biomarkers for response to treatment in the glioblastoma disease setting. In a timely review, John P Lynes and colleagues provide an overview of current efforts toward immunophenotyping glioblastoma as well as establishing the utility of cytokines, immune checkpoints and genetic aberrations as biomarkers for response to treatment. By providing an overview of newer non-invasive imaging and sampling methods and advocating for strategic stratification in clinical trial design, the review offers a perspective on the best path forward to identifying biomarkers that will aid in identifying patients with GBM who will most likely benefit from immunotherapy treatment regimens.

Efficacy of immune checkpoint inhibitors for in-transit melanoma

Emilia Nan Tie, Julia Lai-Kwon, Michael Alexander Rtshiladze, Lumine Na, James Bozzi, Tavis Read, Victoria Atkinson, George Au-Yeung, Georgina Long, Grant A McArthur, Shahneen Sandhu, Robyn Saw, Euan Walpole, Alexander Menzies, Mark Smithers, David E Gyorki
Journal for ImmunoTherapy of Cancer 
2020;8:e000440 (5 May 2020)
Short Report

CCR5 blockade inflames antitumor immunity in BAP1-mutant clear cell renal cell carcinoma

Quan Zhou, Yangyang Qi, Zewei Wang, Han Zeng, Hongyu Zhang, Zhaopei Liu, Qiuren Huang, Ying Xiong, Jiajun Wang, Yuan Chang, Qi Bai, Yu Xia, Yiwei Wang, Li Liu, Le Xu, Bo Dai, Jianming Guo, Yu Zhu, Weijuan Zhang, Jiejie Xu
Journal for ImmunoTherapy of Cancer 
2020;8:e000228 (5 May 2020)
Research

Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG

Sarah Knispel, Andreas Stang, Lisa Zimmer, Hildegard Lax, Ralf Gutzmer, Lucie Heinzerling, Carsten Weishaupt, Claudia Pföhler, Anja Gesierich, Rudolf Herbst, Katharina C Kaehler, Benjamin Weide, Carola Berking, Carmen Loquai, Jochen Utikal, Patrick Terheyden, Martin Kaatz, Max Schlaak, Alexander Kreuter, Jens Ulrich, Peter Mohr, Edgar Dippel, Elisabeth Livingstone, Jürgen C Becker, Michael Weichenthal, Eleftheria Chorti, Janine Gronewold, Dirk Schadendorf, Selma Ugurel
Journal for ImmunoTherapy of Cancer 
2020;8:e000395 (5 May 2020)
Research

Combination immunotherapy induces distinct T-cell repertoire responses when administered to patients with different malignancies

Jason Cham, Li Zhang, Serena Kwek, Alan Paciorek, Tao He, Grant Fong, David Y Oh, Lawrence Fong
Journal for ImmunoTherapy of Cancer 2020;8:e000368  (5 May 2020)
Research

Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial

Lu Xie, Jie Xu, Xin Sun, Wei Guo, Jin Gu, Kuisheng Liu, Bingxin Zheng, Tingting Ren, Yi Huang, Xiaodong Tang, Taiqiang Yan, Rongli Yang, Kunkun Sun, Danhua Shen, Yuan Li
Journal for ImmunoTherapy of Cancer 2020;8:e000798  (5 May 2020)
Research

Paradoxical interaction between cancer and long-term postsepsis disorder: impairment of de novo carcinogenesis versus favoring the growth of established tumors

Caio Abner Leite, Jose Mauricio Mota, Kalil Alves de Lima, Carlos Wagner Wanderley, Leticia Almeida Nascimento, Marcela Davoli Ferreira, Camila Meirelles Souza Silva, David Fernando Colon, Juliana Yumi Sakita, Vinicius Kannen, Paula Ramos Viacava, Maria Dirlei Begnami, Roberto Cesar Pereira Lima-Junior, Vladmir Claudio Cordeiro de Lima, Jose Carlos Alves-Filho, Fernando Queiroz Cunha, Ronaldo Albuquerque Ribeiro
Journal for ImmunoTherapy of Cancer 2020;8:e000129  (5 May 2020)
Research

Heat shock and HSP70 regulate 5-FU-mediated caspase-1 activation in myeloid-derived suppressor cells and tumor growth in mice

Thomas Pilot, Aurélie Fratti, Chloé Thinselin, Anaïs Perrichet, Lucie Demontoux, Emeric Limagne, Valentin Derangère, Alis Ilie, Mané Ndiaye, Elise Jacquin, Carmen Garrido, François Ghiringhelli, Fanny Chalmin, Cédric Rébé
Journal for ImmunoTherapy of Cancer 2020;8:e000478  (7 May 2020)
Research

Overcoming resistance to anti-PD1 and anti-PD-L1 treatment in gastrointestinal malignancies

Alberto Puccini, Francesca Battaglin, Maria Laura Iaia, Heinz-Josef Lenz, Mohamed E Salem
Journal for ImmunoTherapy of Cancer 
2020;8:e000404 (10 May 2020)
Review

Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade

Rui Yang, Samah Elsaadi, Kristine Misund, Pegah Abdollahi, Esten Nymoen Vandsemb, Siv Helen Moen, Anna Kusnierczyk, Geir Slupphaug, Therese Standal, Anders Waage, Tobias S Slørdahl, Torstein Baade Rø, Even Rustad, Anders Sundan, Carl Hay, Zachary Cooper, Alwin G Schuller, Richard Woessner, Alexandra Borodovsky, Eline Menu, Magne Børset, Anne Marit Sponaas
Journal for ImmunoTherapy of Cancer 2020;8:e000610  (14 May 2020)
Research

Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis

Meghan J Mooradian, Daniel Y Wang, Alexandra Coromilas, Melissa Lumish, Tianqi Chen, Anita Giobbie-Hurder, Douglas B. Johnson, Ryan J. Sullivan, Michael Dougan
Journal for ImmunoTherapy of Cancer 2020;8:e000451  (15 May 2020)
Research

Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial

Sandra P D'Angelo, Shailender Bhatia, Andrew S Brohl, Omid Hamid, Janice M Mehnert, Patrick Terheyden, Kent C Shih, Isaac Brownell, Celeste Lebbé, Karl D Lewis, Gerald P Linette, Michele Milella, Sara Georges, Parantu Shah, Barbara Ellers-Lenz, Marcis Bajars, Gülseren Güzel, Paul T Nghiem
Journal for ImmunoTherapy of Cancer 2020;8:e000674  (15 May 2020)
Research

Nivolumab and dinutuximab beta in two patients with refractory neuroblastoma

Karoline Ehlert, Ina Hansjuergens, Andreas Zinke, Sylke Otto, Nikolai Siebert, Guenter Henze, Holger Lode
Journal for ImmunoTherapy of Cancer 2020;8:e000540  (15 May 2020)
Case Report

COVID-19 and lung cancer: risks, mechanisms and treatment interactions

Alfredo Addeo, Michel Obeid, Alex Friedlaender
Journal for ImmunoTherapy of Cancer 2020;8:e000892  (19 May 2020)
Commentary

COVID-19 and immune checkpoint inhibitors: initial considerations

Won Jin HoLudmila DanilovaSu Jin LimRohan VermaStephanie XavierJames M LeathermanMarcelo B SzteinElana J FertigHao WangElizabeth JaffeeMark Yarchoan
Journal for ImmunoTherapy of Cancer 
2020;8:e000933  (19 May 2020)
Commentary

Diffuse pneumonitis from coronavirus HKU1 on checkpoint inhibitor therapy

Michael T Serzan, Princy N Kumar, Michael B Atkins
Journal for ImmunoTherapy of Cancer 
2020;8:e000898 (19 May 2020)
Case Report

PD-L1 targeting high-affinity NK (t-haNK) cells induce direct antitumor effects and target suppressive MDSC populations

Kellsye P Fabian, Michelle R Padget, Renee N. Donahue, Kristen Solocinski, Yvette Robbins, Clint T. Allen, John H. Lee, Shahrooz Rabizadeh, Patrick Soon-Shiong, Jeffrey Schlom, James W Hodge
Journal for ImmunoTherapy of Cancer 
2020;8:e000450 (20 May 2020)
Research

Personalized neoantigen-based immunotherapy for advanced collecting duct carcinoma: case report

Yongyi Zeng, Wei Zhang, Zhenli Li, Youshi Zheng, Yingchao Wang, Geng Chen, Liman Qiu, Kun Ke, Xiaoping Su, Zhixiong Cai, Jingfeng Liu, Xiaolong Liu
Journal for ImmunoTherapy of Cancer 
2020;8:e000676 (20 May 2020)
Case Report

Flow cytometric evaluation of CD38 expression levels in the newly diagnosed T-cell acute lymphoblastic leukemia and the effect of chemotherapy on its expression in measurable residual disease, refractory disease and relapsed disease: an implication for anti-CD38 immunotherapy

Prashant Ramesh Tembhare, Harshini Sriram, Twinkle Khanka, Gaurav Chatterjee, Devasis Panda, Sitaram Ghogale, Yajamanam Badrinath, Nilesh Deshpande, Nikhil V Patkar, Gaurav Narula, Bhausaheb Bagal, Hasmukh Jain, Manju Sengar, Navin Khattry, Shripad Banavali, Sumeet Gujral, Papagudi G Subramanian
Journal for ImmunoTherapy of Cancer
 
2020;8:e000630  (20 May 2020)
Research

Optimized combinatorial pMHC class II multimer labeling for precision immune monitoring of tumor-specific CD4 T cells in patients

Georg Alexander Rockinger, Philippe Guillaume, Amélie Cachot, Margaux Saillard, Daniel E Speiser, Georges Coukos, Alexandre Harari, Pedro J Romero, Julien Schmidt, Camilla Jandus
Journal for ImmunoTherapy of Cancer 2020;8:e000435  (24 May 2020)
Research

Immunomodulatory effects of renin–angiotensin system inhibitors on T lymphocytes in mice with colorectal liver metastases

Dora Lucia Vallejo Ardila, Katrina A Walsh, Theodora Fifis, Rita Paolini, Georgios Kastrappis, Christopher Christophi, Marcos Vinicius Perini
Journal for ImmunoTherapy of Cancer 2020;8:e000487  (24 May 2020)
Research

Efficacy and safety of camrelizumab combined with apatinib in advanced triple-negative breast cancer: an open-label phase II trial

Jieqiong Liu, Qiang Liu, Ying Li, Qian Li, Fengxi Su, Herui Yao, Shicheng Su, Quanren Wang, Liang Jin, Ying Wang, Wan Yee Lau, Zefei Jiang, Erwei Song
Journal for ImmunoTherapy of Cancer 2020;8:e000696  (24 May 2020)
Research

Analytical validation of the Immunoscore and its associated prognostic value in patients with colon cancer

Florence Marliot, Xiaoyi Chen, Amos Kirilovsky, Thomas Sbarrato, Carine El Sissy, Luciana Batista, Marc Van den Eynde, Nacilla Haicheur-Adjouri, Maria-Gabriela Anitei, Ana-Maria Musina, Viorel Scripcariu, Christine Lagorce-Pagès, Fabienne Hermitte, Jérôme Galon, Jacques Fieschi, Franck Pagès
Journal for ImmunoTherapy of Cancer 2020;8:e000272  (24 May 2020)
Research

Cytotoxic T-cell-related gene expression signature predicts improved survival in muscle-invasive urothelial bladder cancer patients after radical cystectomy and adjuvant chemotherapy

Markus Eckstein, Pamela Strissel, Reiner Strick, Veronika Weyerer, Ralph Wirtz, Carolin Pfannstiel, Adrian Wullweber, Fabienne Lange, Philipp Erben, Robert Stoehr, Simone Bertz, Carol Imanuel Geppert, Nicole Fuhrich, Helge Taubert, Sven Wach, Johannes Breyer, Wolfgang Otto, Maximilian Burger, Christian Bolenz, Bastian Keck, Bernd Wullich, Arndt Hartmann, Danijel Sikic
Journal for ImmunoTherapy of Cancer 
2020;8:e000162 (24 May 2020)
Research

Enhanced B7-H4 expression in gliomas with low PD-L1 expression identifies super-cold tumors

Di Chen, Gaopeng Li, Chunxia Ji, Qiqi Lu, Ying Qi, Chao Tang, Ji Xiong, Jian Hu, Fatma Betul Aksoy Yasar, Yan Zhang, Dave S B Hoon, Yu Yao, Liangfu Zhou
Journal for ImmunoTherapy of Cancer 
2020;8:e000154 (25 May 2020)
Research

Temozolomide antagonizes oncolytic immunovirotherapy in glioblastoma

Dipongkor Saha, Samuel D Rabkin, Robert L Martuza
Journal for ImmunoTherapy of Cancer 2020;8:e000345 (25 May 2020)
Research

In-depth plasma proteomics reveals increase in circulating PD-1 during anti-PD-1 immunotherapy in patients with metastatic cutaneous melanoma

Haris Babacic, Janne Lehtiö, Yago Pico de Coaña, Maria Pernemalm, Hanna Eriksson
Journal for ImmunoTherapy of Cancer 
2020;8:e000204 (25 May 2020)
Research

Dual but not single PD-1 or TIM-3 blockade enhances oncolytic virotherapy in refractory lung cancer

Fan Sun, Zong Sheng Guo, Alyssa D Gregory, Steven D Shapiro, Gutian Xiao, Zhaoxia Qu
Journal for ImmunoTherapy of Cancer 
2020;8:e000294 (26 May 2020)
Research

ATR inhibitor AZD6738 enhances the antitumor activity of radiotherapy and immune checkpoint inhibitors by potentiating the tumor immune microenvironment in hepatocellular carcinoma

Hailong Sheng, Yan Huang, Yazhi Xiao, Zhenru Zhu, Mengying Shen, Peitao Zhou, Zeqin Guo, Jian Wang, Hui Wang, Wencong Dai, Wanjun Zhang, Jingyuan Sun, Chuanhui Cao
Journal for ImmunoTherapy of Cancer 
2020;8:e000340 (26 May 2020)
Research

Phase I study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with pretreated biliary tract cancer

Jason Cham, Li Zhang, Serena Kwek, Alan Paciorek, Tao He, Grant Fong, David Y Oh, Lawrence Fong
Journal for ImmunoTherapy of Cancer 2020;8:e000564  (26 May 2020)
Research

Granzyme B is correlated with clinical outcome after PD-1 blockade in patients with stage IV non-small-cell lung cancer

Daan P. Hurkmans, Edwin A. Basak, Nina Schepers, Esther Oomen-De Hoop, Cor H. Van der Leest, Samira El Bouazzaoui, Sander Bins, Stijn L. W. Koolen, Stefan Sleijfer, Astrid A. M. Van der Veldt, Reno Debets, Ron H. N. Van Schaik, Joachim G. J. V. Aerts, Ron H. J. Mathijssen
Journal for ImmunoTherapy of Cancer 2020;8:e000586  (26 May 2020)
Research

NKTR-214 immunotherapy synergizes with radiotherapy to stimulate systemic CD8+ T cell responses capable of curing multi-focal cancer

Hirokazu Matsushita, Kosei Hasegawa, Katsutoshi Oda, Shogo Yamamoto, Kayo Asada, Takahiro Karasaki, Akira Yabuno, Akira Nishijima, Takahide Nejo, Yukari Kobayashi, Sho Sato, Yuji Ikeda, Manami Miyai, Yusuke Takahashi, Rui Yamaguchi, Keiichi Fujiwara, Hiroyuki Aburatani, Kazuhiro Kakimi
Journal for ImmunoTherapy of Cancer 2020;8:e000464  (26 May 2020)
Research

Heterodimeric IL-15 delays tumor growth and promotes intratumoral CTL and dendritic cell accumulation by a cytokine network involving XCL1, IFN-gamma, CXCL9 and CXCL10

Cristina Bergamaschi, Hrishikesh Pandit, Bethany A Nagy, Dimitris Stellas, Shawn M Jensen, Jenifer Bear, Maggie Cam, Antonio Valentin, Bernard A Fox, Barbara K Felber, George N Pavlakis
Journal for ImmunoTherapy of Cancer 2020;8:e000599  (26 May 2020)
Research

Tumor ablation plus co-administration of CpG and saponin adjuvants affects IL-1 production and multifunctional T cell numbers in tumor draining lymph nodes

Tonke K Raaijmakers, Renske J E van den Bijgaart, Martijn H den Brok, Melissa Wassink, Annemarie de Graaf, Jori A Wagenaars, Stefan Nierkens, Marleen Ansems, Gert Jan Scheffer, Gosse J Adema
Journal for ImmunoTherapy of Cancer 
2020;8:e000649 (26 May 2020)
Research

Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma

Brendan Curti, Marka Crittenden, Steven K Seung, Christopher B Fountain, Roxanne Payne, ShuChing Chang, Jessica Fleser, Kimberly Phillips, Ian Malkasian, Lyn B Dobrunick, Walter J Urba
Journal for ImmunoTherapy of Cancer 2020;8:e000773  (27 May 2020)
Research

Interplay between glucocorticoids and tumor-infiltrating lymphocytes on the prognosis of adrenocortical carcinoma

Laura-Sophie Landwehr, Barbara Altieri, Jochen Schreiner, Iuliu Sbiera, Isabel Weigand, Matthias Kroiss, Martin Fassnacht and Silviu Sbiera
Journal for ImmunoTherapy of Cancer 2020;8:e000469  (30 May 2020)
Research

Continuous renal replacement therapy in cytokine release syndrome following immunotherapy or cellular therapies?

Catalin Constantinescu, Sergiu Pasca, Tiberiu Tat, Patric Teodorescu, Catalin Vlad, Sabina Iluta, Delia Dima, Dana Tomescu, Ecaterina Scarlatescu, Alina Tanase, Olafur Eysteinn Sigurjonsson, Anca Colita, Hermann Einsele, Ciprian Tomuleasa
Journal for ImmunoTherapy of Cancer 2020;8:e000742  (30 May 2020)
Hypothesis

CD40 agonist-induced IL-12p40 potentiates hepatotoxicity

Caroline Bonnans, Graham Thomas, Wenqian He, Breanna Jung, Wei Chen, Min Liao, Jonathan Heyen, Bernard Buetow, Smitha Pillai, Diane Matsumoto, Javier Chaparro-Riggers, Shahram Salek-Ardakani, Yan Qu
Journal for ImmunoTherapy of Cancer 2020;8:e000624  (30 May 2020)
Short Report

COVID-19 and lung cancer: risks, mechanisms and treatment interactions

Alfredo Addeo, Michel Obeid, Alex Friedlaender
Journal for ImmunoTherapy of Cancer 2020;8:e000892  (19 May 2020)
Commentary

Tocilizumab, but not dexamethasone, prevents CRS without affecting antitumor activity of bispecific antibodies

Joseph Kauer, Sebastian Hörner, Lukas Osburg, Stefanie Müller, Melanie Märklin, Jonas S Heitmann, Latifa Zekri, Hans-Georg Rammensee, Helmut R Salih, Gundram Jung
Journal for ImmunoTherapy of Cancer 
2020;8:e000621  (30 May 2020)
Short Report

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.