| First Author | Tang Z | Year | 2021 |
| Journal | Cell Rep | Volume | 37 |
| Issue | 11 | Pages | 110111 |
| PubMed ID | 34910922 | Mgi Jnum | J:328788 |
| Mgi Id | MGI:6883798 | Doi | 10.1016/j.celrep.2021.110111 |
| Citation | Tang Z, et al. (2021) Inflammatory macrophages exploit unconventional pro-phagocytic integrins for phagocytosis and anti-tumor immunity. Cell Rep 37(11):110111 |
| abstractText | Blockade of the inhibitory checkpoint SIRPalpha-CD47 promotes phagocytosis of cancer cells by macrophages and is a promising avenue in anti-cancer therapy. Productive phagocytosis is strictly predicated on co-engagement of pro-phagocytic receptors-namely, Fc receptors (FcRs), integrin CD11b, or SLAMF7-by their ligands on cancer cells. Here, we examine whether additional pro-phagocytic receptors could be harnessed to broaden the scope of phagocytosis. Inflammatory stimuli, including multiple cytokines and Toll-like receptor (TLR) ligands, augment phagocytosis efficiency and fully alleviate the requirement of FcRs, CD11b, and SLAMF7 for phagocytosis. These effects are mediated by the unconventional pro-phagocytic integrins CD11a and CD11c, which act with CD18 to initiate actin polarization, leading to phagocytosis. Some inflammatory stimuli enable phagocytosis even in the absence of SIRPalpha-CD47 blockade. Higher CD11c expression in macrophage-enriched tumors correlates with improved survival in clinical studies. Thus, inflammatory macrophages exploit unconventional pro-phagocytic integrins for improved phagocytosis and anti-tumor immunity. |
