Targeting immune checkpoints: how to use natural killer cells for fighting against solid tumors

Natural killer (NK) cells are unique innate immune cells that mediate anti-viral and anti-tumor responses. Thus, they might hold great potential for cancer immunotherapy. NK cell adoptive immunotherapy in humans has shown modest efficacy. In particular, it has failed to demonstrate therapeutic efficiency in the treatment of solid tumors, possibly due in part to the immunosuppressive tumor microenvironment (TME), which reduces NK cell immunotherapy's efficiencies. It is known that immune checkpoints play a prominent role in creating an immunosuppressive TME, leading to NK cell exhaustion and tumor immune escape. Therefore, NK cells must be reversed from their dysfunctional status and increased in their effector roles in order to improve the efficiency of cancer immunotherapy. Blockade of immune checkpoints can not only rescue NK cells from exhaustion but also augment their robust anti-tumor activity. In this review, we discussed immune checkpoint blockade strategies with a focus on chimeric antigen receptor (CAR)-NK cells to redirect NK cells to cancer cells in the treatment of solid tumors.

Automated summary

Natural killer (NK) cells have potential for cancer immunotherapy, but the immunosuppressive tumor microenvironment (TME) hinders their efficacy. Immune checkpoints contribute to NK cell exhaustion and tumor immune escape. Blocking immune checkpoints can rescue exhausted NK cells and enhance their anti-tumor activity. This review focuses on immune checkpoint blockade strategies, particularly using chimeric antigen receptor (CAR)-NK cells, to redirect NK cells to solid tumors.