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Arrested development: suppression of NK cell function in the tumor microenvironment

Luke Riggan1,2, Siya Shah1, Timothy E O'Sullivan1,2

  • 1Department of Microbiology, Immunology, and Molecular Genetics David Geffen School of Medicine at UCLA Los Angeles CA USA.

Clinical & Translational Immunology
|January 18, 2021
PubMed

Insights

Natural killer (NK) cells are crucial for fighting cancer but become dysfunctional in solid tumors. This review explores NK cell dysfunction mechanisms and immunotherapy strategies to restore their anti-cancer activity.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Natural killer (NK) cells are innate lymphocytes with cytotoxic functions against viral infections and tumor metastasis.
  • Dysfunctional and low-count NK cells are prevalent in advanced solid human cancers, impairing anti-tumor immunity.

Purpose of the Study:

  • To review mechanisms of suboptimal NK cell recruitment and function within the tumor microenvironment (TME).
  • To highlight current immunotherapies targeting NK cell dysfunction.
  • To discuss next-generation strategies for adoptive NK cell therapy in solid tumors.

Main Methods:

  • Literature review of mechanisms influencing NK cell function in the TME.
  • Analysis of current immunotherapy approaches for NK cell enhancement.
  • Discussion of future strategies targeting intrinsic and extrinsic checkpoints.

Main Results:

  • The TME harbors factors that impair NK cell recruitment and cytotoxic activity.
  • Current immunotherapies show promise but require optimization.
  • Targeting regulatory checkpoints offers potential for next-generation therapies.

Conclusions:

  • Understanding NK cell dysfunction in the TME is critical for developing effective cancer immunotherapies.
  • Enhancing NK cell function through targeted strategies can improve adoptive cell therapy outcomes.
  • Novel approaches are needed to overcome NK cell suppression in solid tumors.
Keywords:
CRISPRadoptive NK cell therapydysfunctiongenetic engineeringimmunotherapynatural killer cellssuppressiontumor microenvironment

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