Intrinsic and extrinsic factors determining natural killer cell fate: Phenotype and function

Abstract

Natural killer (NK) cells are derived from hematopoietic stem cells. They belong to the innate lymphoid cell family, which is an important part of innate immunity. This family plays a role in the body mainly through the release of perforin, granzyme, and various cytokines and is involved in cytotoxicity and cytokine-mediated immune regulation. NK cells involved in normal immune regulation and the tumor microenvironment (TME) can exhibit completely different states. Here, we discuss the growth, development, and function of NK cells in regard to intrinsic and extrinsic factors. Intrinsic factors are those that influence NK cells to promote cell maturation and exert their effector functions under the control of internal metabolism and self-related genes. Extrinsic factors include the metabolism of the TME and the influence of related proteins on the "fate" of NK cells. This review targets the potential of NK cell metabolism, cellular molecules, regulatory genes, and other mechanisms involved in immune regulation. We further discuss immune-mediated tumor therapy, which is the trend of current research.

Keywords: Cell fate; Cell metabolism; Intrinsic and extrinsic factors; NK cells; Tumor microenvironment.