NK Cell Adoptive Immunotherapy of Cancer: Evaluating Recognition Strategies and Overcoming Limitations

Transplant Cell Ther. 2021 Jan;27(1):21-35. doi: 10.1016/j.bbmt.2020.09.030. Epub 2020 Sep 29.


Natural killer (NK) cells, the primary effector cells of the innate immune system, utilize multiple strategies to recognize tumor cells by (1) detecting the presence of activating receptor ligands, which are often upregulated in cancer; (2) targeting cells that have a loss of major histocompatibility complex (MHC); and (3) binding to antibodies that bind to tumor-specific antigens on the tumor cell surface. All these strategies have been successfully harnessed in adoptive NK cell immunotherapies targeting cancer. In this review, we review the applications of NK cell therapies across different tumor types. Similar to other forms of immunotherapy, tumor-induced immune escape and immune suppression can limit NK cell therapies' efficacy. Therefore, we also discuss how these limitations can be overcome by conferring NK cells with the ability to redirect their tumor-targeting capabilities and survive the immune-suppressive tumor microenvironment. Finally, we also discuss how future iterations can benefit from combination therapies with other immunotherapeutic agents.

Keywords: ADCC; NK activating receptors; NK cell; NK inhibitory receptors; Tumor immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Immunotherapy
  • Immunotherapy, Adoptive*
  • Killer Cells, Natural
  • Neoplasms* / therapy
  • Tumor Microenvironment