The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia.

The immune responses to cancer cells involve both innate and acquired immune cells. In the meantime, the most attention has been drawn to the adaptive immune cells, especially T cells, while, it is now well known that the innate immune cells, especially natural killer (NK) cells, play a vital role in defending against malignancies. While the immune cells are trying to eliminate malignant cells, cancer cells try to prevent the function of these cells and suppress immune responses. The suppression of NK cells in various cancers can lead to the induction of an exhausted phenotype in NK cells, which will impair their function. Recent studies have shown that the occurrence of this phenotype in various types of leukemic malignancies can affect the prognosis of the disease, and targeting these cells may be considered a new immunotherapy method in the treatment of leukemia. Therefore, a detailed study of exhausted NK cells in leukemic diseases can help both to understand the mechanisms of leukemia progression and to design new treatment methods by creating a deeper understanding of these cells. Here, we will comprehensively review the immunobiology of exhausted NK cells and their role in various leukemic malignancies. Video Abstract.