A Natural Impact: NK Cells at the Intersection of Cancer and HIV Disease.

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Despite efficient suppression of plasma viremia in people living with HIV (PLWH) on cART, evidence of HIV-induced immunosuppression remains, and normally benign and opportunistic pathogens become major sources of co-morbidities, including virus-induced cancers. In fact, cancer remains a primary cause of death even in virally suppressed PLWH. Natural killer (NK) cells provide rapid early responses to HIV infection, contribute substantially to disease modulation and vaccine protection, and are also major therapeutic targets for cancer immunotherapy. However, much like other lymphocyte populations, recent burgeoning evidence suggests that in chronic conditions like HIV, NK cells can become functionally exhausted with impaired cytotoxic function, altered cytokine production and impaired antibody-dependent cell-mediated cytotoxicity. Recent work suggests functional anergy is likely due to low-level ongoing virus replication, increased inflammatory cytokines, or increased presence of MHClow target cells. Indeed, HIV-induced loss of NK cell-mediated control of lytic EBV infection has been specifically shown to cause lymphoma and also increases replication of CMV. In this review, we will discuss current understanding of NK cell modulation of HIV disease, reciprocal exhaustion of NK cells, and how this may impact increased cancer incidences and prospects for NK cell-targeted immunotherapies. Finally, we will review the most recent evidence supporting adaptive functions of NK cells and highlight the potential of adaptive NK cells for cancer immunotherapy.





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Lucar, Olivier, R Keith Reeves and Stephanie Jost (2019). A Natural Impact: NK Cells at the Intersection of Cancer and HIV Disease. Frontiers in immunology, 10(AUG). p. 1850. 10.3389/fimmu.2019.01850 Retrieved from https://hdl.handle.net/10161/27269.

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Roger Keith Reeves

Professor in Surgery

Formerly of Harvard Medical School and Beth Israel Deaconess Medical Center, Dr. R. Keith Reeves is currently tenured Professor of Surgery at Duke University, as well as Director of the Division of Innate and Comparative Immunology and Head of Innovation Partnerships in the Center for Human Systems Immunology. He is also currently the Director of the Duke CFAR Developmental Core and Editor-in-Chief of AIDS Research and Human Retroviruses. Over his academic career he has published extensively in the field of NK cell biology, providing some of the most comprehensive analyses of NK cells and innate lymphoid cells, including the first characterization of memory NK cells in any primate species.  Dr. Reeves’ research has been supported by NIH for over a decade by individual and consortia grants, and in addition to independent work, he collaborates as part of the HIV Vaccine Trials Network (HVTN) and the BEAT-HIV Martin Delaney HIV Cure Collaboratory.   Dr. Reeves has also served on multiple standing NIH study sections (HIV Immunopathogenesis and Vaccine Development), as well as on standing and ad hoc grant review committees for amfAR, the United States-Israel Binational Science Foundation, the UK Medical Research Council and California Institute of Regenerative Medicine, among others.   Considered a global expert in NK cell biology, Dr. Reeves’ group continues to focus on cutting edge approaches to harness NK cells in the context of vaccines and antiviral therapeutics for HIV, CMV, HCV, influenza and SARSCoV2.


Stephanie Rachel Jost

Associate Professor in Surgery

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