In recent years, the anti-PD-1/PD-L1 blockade has become a game changer in cancer treatment following the unprecedented response rate. Regardless of the substantial therapy efficacy across various cancer types, some patients do not still respond to these therapies, indicating that a deeper understanding of the mechanisms of anti-PD-1/PD-L1 resistance is highly important. To overcome such resistance, the tumor-induced immunosuppressive mechanisms have been focused and several suppressor cell populations in the tumor microenvironment have been identified. Among these cells, macrophages, neutrophils, and mast cells are known to play key roles in anti-PD-1/PD-L1 resistance. Hence, gaining control over these innate immune cells can open opportunities for breaking tumor resistance to immune checkpoint inhibitors. Herein, a summary of the role of macrophages, neutrophils, and mast cells in anti-PD-1/PD-L1 resistance has been described. Also, strategies to overcome their therapeutic resistance to anti-PD-1/PD-L1 have been discussed.
Keywords: Anti-PD-L1/PD-1; Immune checkpoint blockade; Tumor-associated macrophages; Tumor-associated mast cells; Tumor-associated neutrophils.
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.