PD-L1 and PD-1 binding is an important pathway for tumor immune escape. Therefore, antibody drugs targeting PD-L1\PD-1 have become popular drugs for relieving immunosuppression and treating tumors. However, in a prostate cancer, the expression level of PD-L1 is very low, so it usually does not respond to PD-L1 antibodies.
Recently, it has been reported that in prostate cancer, the expression level of PD-L1 is very low, because the part of PD-L1 which is translated in the cell is encapsulated into the vesicle and released into the extracellular, and the vesicle is mainly exosomes.
The authors knocked out Rab27a and nSMase2 on PC3 cells (the key proteins that control the secretion and secretion of exosomes), and found that cells lacking exosomes,IL-2 was be secreted in large amounts for cells lacking exosomes, indicating that T cells are activated. When the exosomes of PC3 were introduced, the secretion of IL-2 could be re-suppressed, indicating that PC3 exosomes inhibit T cell activity.
The authors further used the TRAMP-C2 model to verify the function of Exosomal PD-L1 in vivo. The results indicate that Rab27a, nSMase2, and PD-L1 promote tumor growth by inhibiting the immune system.
By further clustering CD8+, CD4+ T cells with T cell fatigue and activated markers, the results showed that T lymphocytes of Rab27a null and Pd-l1 null TRAMP-C2 cells were significantly activated. Tumor cells inhibit the activation of T cells by exosomal PD-L1
The authors subcutaneously injected Rab27a null or PD-L1 null TRAMP-C2 cells into C57BL6/J mice, and found that in the absence of exosomal PD-L1, immune-sound mice not only directly inhibit tumor cells edited by these genes and it also be able to produce memory for tumor cells.
Through the above experiments, it has been basically confirmed that knocking out Rab27a to inhibit exosomes secretion, or knocking out PD-L1 can directly or at the distal end to relieve immunosuppression and inhibit tumor growth. A role for exosomal PD-L1 is also seen in a syngeneic colorectal model.

REFERENCES:Poggio et al. (2019) Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory. Cell 177(2): 414–427.