Mechanisms of NK cell dysfunction in the tumor microenvironment and current clinical approaches to harness NK cell potential for immunotherapy

J Leukoc Biol. 2021 Jun;109(6):1071-1088. doi: 10.1002/JLB.5MR0920-198RR. Epub 2020 Sep 29.

Abstract

NK cells are innate immune cells with inherent capabilities in both recognizing and killing cancer cells. NK cell phenotypes and functional alterations are being described with increasing precision among patients harboring various cancer types, emphasizing the critical role that NK cells play in antitumor immune responses. In addition, advances in understanding NK cell biology have improved our knowledge of such alterations, thereby expanding the potential exploitation of NK cells' anticancer capabilities. In this review, we present an overview of (1) the various types of NK cell alterations that may contribute to immune evasion in cancer patients and (2) the various strategies to improve NK cell-based anticancer immunotherapies, including pharmacologic modulation and/or genetic modification.

Keywords: CAR; NK cells; cancer immunotherapy; checkpoint inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Combined Modality Therapy
  • Humans
  • Immunotherapy* / adverse effects
  • Immunotherapy* / methods
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Treatment Outcome
  • Tumor Escape / immunology
  • Tumor Microenvironment / immunology*