Figure 4.

Immunotherapy strategies based on innate immune cells. Various tumor treatment regimens can be implemented by boosting the effector functions of innate immune cells, including generating engineered CAR NK cells with high anti-tumor activity and CAR macrophages which can be polarized towards an anti-tumor M1 phenotype, developing anti-tumor antibodies that can bind to activating FcRs expressed on innate immune cells lacking antigen receptors, and enabling them to act specifically on EC cells, and targeting toll-like receptors (TLRs) and RIG-I-like receptors (RLRs), to generate a ‘pathogen-induced-like’ innate immune responses at the tumor site, since the innate immune system can sense the nucleic acids of growing tumors using the pathogen and damage receptors involved in infection detection. Another immunotherapy strategy is to control immunosuppression signals on innate immune cells via development of broad-spectrum immune checkpoint inhibitors targeting NK cells (i.e., LAG3, TIM3, and PD-1, which we review here, and NKG2A, CTLA4, TIGIT, and CD96 which require further investigation) and/or myeloid cells (i.e., SIRPα).