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Masters of Immunology

Priority Briefs

  • Priority Briefs | AuthorChoice
    Combined BRAF, MEK, and CDK4/6 Inhibition Depletes Intratumoral Immune-Potentiating Myeloid Populations in Melanoma
    Emily J. Lelliott, Stefano Mangiola, Kelly M. Ramsbottom, Magnus Zethoven, Lydia Lim, Peter K.H. Lau, Amanda J. Oliver, Luciano G. Martelotto, Laura Kirby, Claire Martin, Riyaben P. Patel, Alison Slater, Carleen Cullinane, Anthony T. Papenfuss, Nicole M. Haynes, Grant A. McArthur, Jane Oliaro and Karen E. Sheppard
    Cancer Immunol Res February 1 2021 9 (2) 136-146; DOI:10.1158/2326-6066.CIR-20-0401

    Combined BRAF, MEK, and CDK4/6 inhibition is being tested in clinical trials for treating melanoma. The authors show this combination depletes tumor-associated myeloid cells in the tumor immune microenvironment, which renders tumors unresponsive to immune checkpoint blockade.

  • Priority Briefs
    Kindlin3-Dependent CD11b/CD18-Integrin Activation Is Required for Potentiation of Neutrophil Cytotoxicity by CD47–SIRPα Checkpoint Disruption
    Panagiota Bouti, Xi Wen Zhao, Paul J.J.H. Verkuijlen, Anton T.J. Tool, Michel van Houdt, Nezihe Köker, Mustafa Yavuz Köker, Ozlem Keskin, Sinan Akbayram, Robin van Bruggen, Taco W. Kuijpers, Hanke L. Matlung and Timo K. van den Berg
    Cancer Immunol Res February 1 2021 9 (2) 147-155; DOI:10.1158/2326-6066.CIR-20-0491

    Neutrophil-mediated ADCC is dependent on CD11b/CD18-integrin–mediated conjugate formation and is controlled by CD47–SIRPα signaling. By using LAD3-derived neutrophils, it is demonstrated that CD47–SIRPα signaling controls CD11b/CD18-integrin inside-out activation during conjugate formation in a kindlin3-dependent manner.

Research Articles

  • Research Articles
    KIR3DL3 Is an Inhibitory Receptor for HHLA2 that Mediates an Alternative Immunoinhibitory Pathway to PD1
    Rupal S. Bhatt, Abdulla Berjis, Julie C. Konge, Kathleen M. Mahoney, Alyssa N. Klee, Samuel S. Freeman, Chun-Hau Chen, Opeyemi A. Jegede, Paul J. Catalano, Jean-Christophe Pignon, Maura Sticco-Ivins, Baogong Zhu, Ping Hua, Jo Soden, Jie Zhu, David F. McDermott, Antonio R. Arulanandam, Sabina Signoretti and Gordon J. Freeman
    Cancer Immunol Res February 1 2021 9 (2) 156-169; DOI:10.1158/2326-6066.CIR-20-0315

    The B7 family member HHLA2 delivers costimulatory signals via TMIGD2. The data show that KIR3DL3 is an inhibitory receptor for HHLA2 and that HHLA2 is expressed in kidney cancer separately from PDL1; targeting this interaction could be immunotherapeutic.

  • Research Articles
    Nutlin-3a Enhances Natural Killer Cell–Mediated Killing of Neuroblastoma by Restoring p53-Dependent Expression of Ligands for NKG2D and DNAM-1 Receptors
    Irene Veneziani, Paola Infante, Elisa Ferretti, Ombretta Melaiu, Cecilia Battistelli, Valeria Lucarini, Mirco Compagnone, Carmine Nicoletti, Aurora Castellano, Stefania Petrini, Marzia Ognibene, Annalisa Pezzolo, Lucia Di Marcotullio, Roberto Bei, Lorenzo Moretta, Vito Pistoia, Doriana Fruci, Vincenzo Barnaba, Franco Locatelli and Loredana Cifaldi
    Cancer Immunol Res February 1 2021 9 (2) 170-183; DOI:10.1158/2326-6066.CIR-20-0313

    Nutlin-3a, a small molecule antagonizing the inhibitory MDM2–p53 interaction, has a p53-dependent immunomodulatory effect on neuroblastoma. Nutlin-3a increases neuroblastoma's susceptibility to NK-cell killing, highlighting how this compound could be prospectively employed for an NK cell–based immunotherapy.

  • Research Articles
    Pharmacologic Screening Identifies Metabolic Vulnerabilities of CD8+ T Cells
    Jefte M. Drijvers, Jacob E. Gillis, Tara Muijlwijk, Thao H. Nguyen, Emily F. Gaudiano, Isaac S. Harris, Martin W. LaFleur, Alison E. Ringel, Cong-Hui Yao, Kiran Kurmi, Vikram R. Juneja, Justin D. Trombley, Marcia C. Haigis and Arlene H. Sharpe
    Cancer Immunol Res February 1 2021 9 (2) 184-199; DOI:10.1158/2326-6066.CIR-20-0384

    It is challenging to develop metabolism-targeted therapeutics because T cells and cancer cells have similar metabolic properties. The authors develop an in vitro pharmacologic screening platform and highlight ferroptosis as a metabolic vulnerability of CD8+ T cells.

  • Research Articles
    Targeted Deletion of CXCR2 in Myeloid Cells Alters the Tumor Immune Environment to Improve Antitumor Immunity
    Jinming Yang, Chi Yan, Anna E. Vilgelm, Sheau-Chiann Chen, Gregory D. Ayers, Christopher A. Johnson and Ann Richmond
    Cancer Immunol Res February 1 2021 9 (2) 200-213; DOI:10.1158/2326-6066.CIR-20-0312

    Myeloid cell CXCR2 affects not only suppressive MDSCs but also B cells, especially the B1b subset. CXCL11-producing B cells are key and impact infiltration and activation of effector CD8+ T cells in the tumor microenvironment.

  • Research Articles
    Oxidized Lipoproteins Promote Resistance to Cancer Immunotherapy Independent of Patient Obesity
    Niloufar Khojandi, Lindsey M. Kuehm, Alexander Piening, Maureen J. Donlin, Eddy C. Hsueh, Theresa L. Schwartz, Kaitlin Farrell, John M. Richart, Elizabeth Geerling, Amelia K. Pinto, Sarah L. George, Carolyn J. Albert, David A. Ford, Xiufen Chen, Justin Kline and Ryan M. Teague
    Cancer Immunol Res February 1 2021 9 (2) 214-226; DOI:10.1158/2326-6066.CIR-20-0358

    The influence of obesity on cancer immunotherapy is not clear. This study shows oxidized LDL promotes resistance to immunotherapy by suppressing T-cell function and driving tumor cytoprotection mediated by heme oxygenase-1 (HO-1), suggesting HO-1 is a promising therapeutic target.

  • Research Articles
    Fructose Promotes Cytoprotection in Melanoma Tumors and Resistance to Immunotherapy
    Lindsey M. Kuehm, Niloufar Khojandi, Alexander Piening, Lauryn E. Klevorn, Simone C. Geraud, Nicole R. McLaughlin, Kristine Griffett, Thomas P. Burris, Kelly D. Pyles, Afton M. Nelson, Mary L. Preuss, Kevin A. Bockerstett, Maureen J. Donlin, Kyle S. McCommis, Richard J. DiPaolo and Ryan M. Teague
    Cancer Immunol Res February 1 2021 9 (2) 227-238; DOI:10.1158/2326-6066.CIR-20-0396

    Dietary fructose can be utilized by tumor cells and promotes cytoprotection by inducing HO-1 expression, thereby impacting TIL responses and immunotherapy outcomes. The data highlight a novel immune evasion mechanism and a potential therapeutic target.

  • Research Articles
    Therapy of Established Tumors with Rationally Designed Multiple Agents Targeting Diverse Immune–Tumor Interactions: Engage, Expand, Enable
    Kellsye P. Fabian, Anthony S. Malamas, Michelle R. Padget, Kristen Solocinski, Benjamin Wolfson, Rika Fujii, Houssein Abdul Sater, Jeffrey Schlom and James W. Hodge
    Cancer Immunol Res February 1 2021 9 (2) 239-252; DOI:10.1158/2326-6066.CIR-20-0638

    Treatment of established tumors with a combination “pentatherapy” regimen leads to T-cell activation while decreasing Treg suppression. The data highlight how the combination of multimodal immunotherapy agents can engage, enhance, and enable adaptive antitumor responses.

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