Fig. 1.

Schematic of cancer immunity cycle with diverse cancer treatment paradigms. The cells involved in each step of the cancer immunity circle face various conditions including inhibition and stimulation. Tumor-associated antigens (TAAs) are released, followed by their uptake and presentation by professional antigen-presenting cells (e.g., dendritic cells (DCs)), boosting DCs maturation. These processes are inhibited by immunosuppressive cytokines (IL-4, IL-10, and IL-13). Mature DCs subsequently migrate to the lymphoid organs and activate naive T cells. The activated T cells are suppressed by physiological conditions in the tumor microenvironment (TME), indoleamine 2,3-dioxygenase (IDO)-expressing cells, myeloid-derived suppressor cells (MDSCs), Treg cells, tumor-associated macrophages (TAM), and immune checkpoint molecules (PD-1, PD-L1). Thus, CAR-T cells are trained and stimulated ex vivo to enhance the antigen-specific antitumor responses after infusion to patients. ICB therapy results in synergistic effects to enhance the tumor infiltration by cytotoxic T lymphocytes (CTLs) and tumor-killing effects