Fig. 3.

Application strategy of CAR-NK cells in tumor combination therapy. The TME is the major hindrance of CAR-NK therapy due to many factors such as immunosuppressive components secreted by a variety of inhibitory cells in the TME. Overcoming the immunosuppressive function of the TME in CAR-NK therapy is the key point to be considered for combination therapy, such as anti-PD-1/PD-L1, chemotherapy, kinase inhibitors, proteasome inhibitors, STING agonist, oncolytic virus, photothermal therapy. These methods can stimulate the release of tumor antigens and DAMPs, thus promoting the initiation, expansion and killing of CAR-NK cells. Numerous targetable molecules exist that can be categorized as TSA, TAA, CASC expressed antigen.