Exosomal PD L1 harbors active defense function to suppress T cell activity and promote breast cancer tumor growth.

Tumor cell-derived exosomes play important roles in tumor-microenvironment regulations, and PD-L1 plays a passive protective role in the tumor microenvironment for tumor growth and progression. Our research revealed that PD-L1 exists in exosomes derived from human and mouse breast cancer cells and can be transferred to other cancer cells, rendering PD-L1-negative cancer cells PD-L1 positive and escape from T-cell killing. By binding to its receptor PD-1 to inhibit T-cell antitumor function, exosomal PD-L1 from cancer cells harbors active defense function to protect and promote tumor growth of breast cancer cells. Together with both genetic approach and pharmacologic inhibitor, the results suggested that blockage of exosome-PD-L1 secretion likely contribute significantly to antitumor immunity, and the combined inhibition of exosome secretion and anti-PD-L1 therapy has the potential to improve antitumor response in the clinic. Citation Format: Yi Yang, Chia-Wei Li, Li-Chuan Chan, Yongkun Wei, Jung-Mao Hsu, Weiya Xia, Jong-Ho Cha, Junwei Hou, Jennifer L. Hsu, Linlin Sun, Mien-Chie Hung. Exosomal PD-L1 harbors active defense function to suppress T-cell activity and promote breast cancer tumor growth [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B17.