Abstract
The continuous, in-depth exploration of the occurrence and development of cancer has shown that immune cell dysfunction is closely associated with tumor progression and poor clinical prognosis. The inhibition of the effector functions of immune cells by numerous immunosuppressive factors in the tumor microenvironment (TME) promotes the progression and metastasis of malignant tumors. Natural killer (NK) cells are the main effector cells in the anti-tumor innate immune system. Dysfunctional NK cells, characterized as weakened proliferation capacity and reduced production of effector cytokines, have limited ability to kill malignant cells and inhibit tumor progression. The reversal of the dysfunctional state of NK cells and enhancement of their effector functions is a promising strategy that could improve the effectiveness of cancer immunotherapy. In order to fully use of the cytotoxic effects of NK cells and revitalize the anti-tumor potential of NK cells in tumor patients, it is necessary to learn more about the characteristics of NK cell dysfunction in TME. This will provide valuable information for the development of personalized strategies to restore anti-tumor immunity. Here, we reviewed the characteristics of dysfunctional NK cells in the TME and latest progress in research, and discussed promising immunotherapy strategies that could utilize NK cell potential for cancer immunotherapy.