Fig. 2

Phagocytosis checkpoints in cancer immunotherapy. Phagocytosis of tumor cells by macrophages is regulated by many “eat me” (pro-phagocytosis) and “don’t eat me” (anti-phagocytosis) signals. The expression of “don’t eat me” signals on tumor cells including CD47, CD24, PD-L1, MHC-I and STC-1 protect tumor cells from phagocytic clearance by interacting with their receptors on phagocytes. The working pathways are CD47-SIRPα, CD24-Siglec-10, MHC-1(B2M)-LILRB1, and PD-L1-PD-1. The high expression of tumor STC-1 traps the calreticulin in mitochondria and ER thus reducing the quantity of calreticulin on the cell surface, impairing phagocytosis and antigen processing and presentation, also leading to weak T cell response. Other anti-phagocytosis receptors such as SLAMF3, SLAMF4, FcγRIIB, and CLEC-1 facilitate the phagocytosis of tumor cells by phagocytes. The “eat me” signals such as calreticulin bind with the membrane glycans and are located on the cancer cell surface. It interacts with the lipoprotein receptor-related protein 1 (LRP1) receptor present on phagocytes. It seems that SLAMF7 expressed on tumor cells and MAC-1 on macrophages are both critical for inducing tumor phagocytosis, while the clear mechanism of SLAMF7-induced phagocytosis is under investigation