Inflammatory macrophages exploit unconventional pro-phagocytic integrins for phagocytosis and anti-tumor immunity.
Cell Rep
; 37(11): 110111, 2021 12 14.
Article
en En
| MEDLINE
| ID: mdl-34910922
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Peritoneales
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Fagocitosis
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Antígeno CD11a
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Antígeno CD11c
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Familia de Moléculas Señalizadoras de la Activación Linfocitaria
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Inflamación
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Macrófagos
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article