The following articles have been recommended for further reading in the field of cancer immunotherapy by JITC’s Commentary/Editorials Section Editor, Christian Capitini.
“Gene Regulatory Programs Conferring Phenotypic Identities to Human NK Cells,” by Patrick L. Collins et al. Cell 2018 Dec 27; 176(1):348-360
While natural killer (NK) cells are known to play an important role in tumor surveillance, there remains a lack of understanding as to how they regulate clinical efficacy through cytotoxicity, IFNy production, homing, proliferation, self-renewal, and memory. Collins et al. presents an integrated analysis of human NK subsets, revealing super-enhancers associated with gene cohorts that may coordinate NK functions and localization. This study provides integrative and single cell analyses, revealing potential developmental relationships between circulating NK cells and implicates a major clinical role for the use of NK cells in cellular therapies, especially those with a memory or adaptive phenotype.
“Anti-NKG2A mAb is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells,” by Pascale Andre et al. Cell 2018 Dec 13; 175(7):1731-1743.e13
While checkpoint immunotherapy has yielded unprecedented results in patients with advanced stage cancers, only a fraction of patients experience a strong response, leading investigators to examine mechanisms of resistance, novel molecular targets and combination therapies. Andre et al. characterizes the first-in-class immune checkpoint inhibitor, monalizumab, which targets NKG2A to promote anti-tumor immunity by enhancing the activities of both T and NK cells. This study demonstrates how NKG2A blockade enhances the anti-tumor immunity mediated by NK and CD8+ T cells when used as both a single agent or in combination with other monoclonal antibodies and highlights the potential of critical immune checkpoints other than PD-1 and CTLA-4.
“CAR T cells targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors,” by Robbie G. Majzner et al. Clin Cancer Res 2019 Jan 17
Although chimeric antigen receptor (CAR) T cells have seen great success in treating relapsed pediatric patients with leukemias, lymphomas and localized sarcomas, this has yet to be translated to solid tumors, due in part to a lack of targetable cell surface molecules. Majzner et al. presents pre-clinical data demonstrating significant anti-tumor potential and clear tumor regression following treatment with B7-H3 (CD276) CAR T cells in in vivo models of osteosarcoma, medulloblastoma and Ewing sarcoma. Thus, in detailing a novel CAR directed at B7-H3, a pan-cancer antigen expressed on many pediatric solid tumors, this study provides promising data for early phase clinical trials.
“IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses,” by Rosa M. Santana Carrero et al. Proc Natl Acad Sci USA 2019 Jan 8; 116(2):599-608
IL-15 is a cytokine that preferentially stimulates CD8+ T cell and NK cell activation, proliferation, and cytolytic activity. While correlative data implicate IL-15 expression within the tumor microenvironment as a critical factor in modulating antitumor responses, the mechanisms regulating IL-15 within tumors are unknown. Carrerro et al. provides evidence that IL-15 is present within the tumor microenvironment, is regulated by inflammatory signals, and importantly, is capable of enhancing tumor regression through a natural mechanism within tumors that works to enhance antitumor responses. This study supports evaluation of systemic treatments with IL-15 or IL-15 analogs as potential cancer therapeutics.
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