2017 May 25; 545(7655): 495–499 | Sydney R. Gordon, Roy L. Maute, Ben W. Dulken, Gregor Hutter, Benson M. George, Melissa N. McCracken, Rohit Gupta, Jonathan M. Tsai, Rahul Sinha, Daniel Corey, Aaron M. Ring, Andrew J. Connolly, and Irving L. Weissman
The study investigates the role of programmed cell death protein 1 (PD-1) expression on tumor-associated macrophages (TAMs) in tumor immunity. PD-1 is an immune checkpoint receptor that, when upregulated on activated T cells, induces immune tolerance. The authors found that both mouse and human TAMs express PD-1, with expression increasing over time in mouse models and with disease progression in primary human cancers. PD-1 expression on TAMs negatively correlates with their phagocytic ability against tumor cells. In vivo studies showed that blocking the PD-1/PD-L1 pathway increased TAM phagocytosis, reduced tumor growth, and improved survival in mouse models of cancer. The results suggest that PD-1/PD-L1 therapies may also affect TAM function, providing new insights into the mechanisms of anti-tumor immunity and potential treatment combinations.The study investigates the role of programmed cell death protein 1 (PD-1) expression on tumor-associated macrophages (TAMs) in tumor immunity. PD-1 is an immune checkpoint receptor that, when upregulated on activated T cells, induces immune tolerance. The authors found that both mouse and human TAMs express PD-1, with expression increasing over time in mouse models and with disease progression in primary human cancers. PD-1 expression on TAMs negatively correlates with their phagocytic ability against tumor cells. In vivo studies showed that blocking the PD-1/PD-L1 pathway increased TAM phagocytosis, reduced tumor growth, and improved survival in mouse models of cancer. The results suggest that PD-1/PD-L1 therapies may also affect TAM function, providing new insights into the mechanisms of anti-tumor immunity and potential treatment combinations.