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Chester C, Fritsch K, Kohrt HE. Natural Killer Cell Immunomodulation: Targeting Activating, Inhibitory, and Co-stimulatory Receptor Signaling for Cancer Immunotherapy. Front Immunol. 2015;6:601doi: 10.3389/fimmu.2015.00601.
Chester, C., Fritsch, K., & Kohrt, H. E. (2015). Natural Killer Cell Immunomodulation: Targeting Activating, Inhibitory, and Co-stimulatory Receptor Signaling for Cancer Immunotherapy. Frontiers in immunology, 6601. https://doi.org/10.3389/fimmu.2015.00601
Chester, Cariad, et al. "Natural Killer Cell Immunomodulation: Targeting Activating, Inhibitory, and Co-stimulatory Receptor Signaling for Cancer Immunotherapy." Frontiers in immunology vol. 6 (2015): 601. doi: https://doi.org/10.3389/fimmu.2015.00601
Chester C, Fritsch K, Kohrt HE. Natural Killer Cell Immunomodulation: Targeting Activating, Inhibitory, and Co-stimulatory Receptor Signaling for Cancer Immunotherapy. Front Immunol. 2015 Dec 02;6:601. doi: 10.3389/fimmu.2015.00601. eCollection 2015. PMID: 26697006; PMCID: PMC4667030.
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Front Immunol. 2015 Dec 02;6:601. doi: 10.3389/fimmu.2015.00601. eCollection 2015.

Natural Killer Cell Immunomodulation: Targeting Activating, Inhibitory, and Co-stimulatory Receptor Signaling for Cancer Immunotherapy.

Frontiers in immunology

Cariad Chester, Katherine Fritsch, Holbrook E Kohrt

Affiliations

  1. Division of Oncology, Department of Medicine, Stanford University , Stanford, CA , USA ; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine , Stanford, CA , USA.
  2. Division of Oncology, Department of Medicine, Stanford University , Stanford, CA , USA.

PMID: 26697006 PMCID: PMC4667030 DOI: 10.3389/fimmu.2015.00601

Abstract

There is compelling clinical and experimental evidence to suggest that natural killer (NK) cells play a critical role in the recognition and eradication of tumors. Efforts at using NK cells as antitumor agents began over two decades ago, but recent advances in elucidating NK cell biology have accelerated the development of NK cell-targeting therapeutics. NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors. In the early phases of cancer immune surveillance, NK cells directly identify and lyse cancer cells. Nascent transformed cells elicit NK cell activation and are eliminated. However, as tumors progress, cancerous cells develop immunosuppressive mechanisms that circumvent NK cell-mediated killing, allowing for tumor escape and proliferation. Therapeutic intervention aims to reverse tumor-induced NK cell suppression and sustain NK cells' tumorlytic capacities. Here, we review tumor-NK cell interactions, discuss the mechanisms by which NK cells generate an antitumor immune response, and discuss NK cell-based therapeutic strategies targeting activating, inhibitory, and co-stimulatory receptors.

Keywords: adoptive cell therapy; cancer vaccines; checkpoint blockade; immunotherapy; monoclonal antibody; natural killer cells

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