Immune Circuits to Shape Natural Killer Cells in Cancer

SIMPLE SUMMARY: Natural killer (NK) cells are circulating innate lymphocytes endowed with antitumoral functions. NK cells are the innate counterpart of effector T cells and among the first cells responding to infections and tumors. In this review, the immune circuits regulating the NK cell antitumoral functions and the possible strategies to shape natural killing in cancer will be discussed. ABSTRACT: Natural killer (NK) cells are innate lymphoid cells playing an important role in anti-cancer immunity. NK cells are efficient in controlling the spreading of metastasis but are not very powerful in fighting against primary tumors. The NK cell capability to infiltrate and persist in the tumor microenvironment and to exert their antitumoral functions is often limited by tumor escape mechanisms. These tumor-mediated strategies not only induce NK cell tolerance but also interfere with the NK cell-dependent immune networking. This review will provide an overview of the tumor escape mechanisms impacting NK cells, identify the immune circuits regulating the NK cell-dependent antitumor immunity and revise the emerging therapeutic approaches to unleash NK cells in cancer.