Innate immune cells in tumor microenvironment: A new frontier in cancer immunotherapy.

Innate immune cells, crucial in resisting infections and initiating adaptive immunity, play diverse and significant roles in tumor development. These cells, including macrophages, granulocytes, dendritic cells (DCs), innate lymphoid cells, and innate-like T cells, are pivotal in the tumor microenvironment (TME). Innate immune cells are crucial components of the TME, based on which various immunotherapy strategies have been explored. Immunotherapy strategies, such as novel immune checkpoint inhibitors, STING/CD40 agonists, macrophage-based surface backpack anchoring, polarization approaches, DC-based tumor vaccines, and CAR-engineered innate immune cells, aim to enhance their anti-tumor potential and counteract cancer-induced immunosuppression. The proximity of innate immune cells to tumor cells in the TME also makes them excellent drug carriers. In this review, we will first provide a systematic overview of innate immune cells within the TME and then discuss innate cell-based therapeutic strategies. Furthermore, the research obstacles and perspectives within the field will also be addressed.