Tumor-Associated Macrophages Regulate PD-1/PD-L1 Immunosuppression

• Published in: Frontiers in immunology Vol. 13; p. 874589
• Main Authors: Pu, Yunzhou, Ji, Qing
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 03.05.2022
• Subjects: B7-H1 Antigen - metabolism; Humans; immune checkpoint inhibitor (ICI); Immune Checkpoint Inhibitors; immune microenvironment; Immunology; immunosuppression; Immunosuppression Therapy; PD-1/PD-L1 axis; Programmed Cell Death 1 Receptor; Tumor Microenvironment; Tumor-Associated Macrophages; tumor-associated macrophages (TAMs); immunosuppression; immune microenvironment; immune checkpoint inhibitor (ICI); tumor-associated macrophages (TAMs); PD-1/PD-L1 axis
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.874589

Anti-programmed cell death 1 (PD-1) or anti-PD-ligand (L) 1 drugs, as classic immune checkpoint inhibitors, are considered promising treatment strategies for tumors. In clinical practice, some cancer patients experience drug resistance and disease progression in the process of anti-PD-1/PD-L1 immunotherapy. Tumor-associated macrophages (TAMs) play key roles in regulating PD-1/PD-L1 immunosuppression by inhibiting the recruitment and function of T cells through cytokines, superficial immune checkpoint ligands, and exosomes. There are several therapies available to recover the anticancer efficacy of PD-1/PD-L1 inhibitors by targeting TAMs, including the inhibition of TAM differentiation and re-education of TAM activation. In this review, we will summarize the roles and mechanisms of TAMs in PD-1/PD-L1 blocker resistance. Furthermore, we will discuss the therapies that were designed to deplete TAMs, re-educate TAMs, and intervene with chemokines secreted by TAMs and exosomes from M1 macrophages, providing more potential options to improve the efficacy of PD-1/PD-L1 inhibitors.