Inflammatory macrophages exploit unconventional pro-phagocytic integrins for phagocytosis and anti-tumor immunity.

Abstract	Blockade of the inhibitory checkpoint SIRPα-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 SIRPα-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.
Authors	Zhenghai Tang, Dominique Davidson, Rui Li, Ming-Chao Zhong, Jin Qian, Jun Chen, André Veillette
Journal	Cell reports (Cell Rep) Vol. 37 Issue 11 Pg. 110111 (12 14 2021) ISSN: 2211-1247 [Electronic] United States
PMID	34910922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References	CD11a Antigen CD11c Antigen Signaling Lymphocytic Activation Molecule Family Slamf7 protein, mouse
Topics	Animals CD11a Antigen (genetics, metabolism) CD11c Antigen (genetics, metabolism) Female Inflammation (immunology) Macrophages (immunology) Male Mice Mice, Inbred C57BL Mice, Knockout Peritoneal Neoplasms (immunology, metabolism, pathology, prevention & control) Phagocytosis Signaling Lymphocytic Activation Molecule Family (physiology)

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