Exosomal PDL1 Suppresses the Anticancer Activity of CD8+ T Cells in Hepatocellular Carcinoma.

Abstract

Tumor microenvironment (TME) is essential for the development and progression of hepatocellular carcinoma (HCC). Exosomes participate in constructing TME by passing biological information, but the regulatory effect of PDL1 in exosomes on anticancer activity of CD8⁺ T cells in HCC still needs to be further explored. In this study, high level of PDL1 was found in plasma exosomes of HCC patients, which turned out to be significantly associated with the increased number of tumor nodules, the upregulated level of serum AFP, the raised tendency of TNM stage, and the poor prognosis of HCC. The expression of CD8 may be inhibited in HCC that is characterized with high level of PDL1, and the protein level of exosomal PDL1 was determined by intracellular PDL1 abundance. High level of exosomal PDL1 inhibited the proliferation and activation of CD8⁺ T cells, but exhibited limited effect on the proliferation of hepatic cancer cells. Moreover, the growth of tumors formed by hepatic cancer cells Hepa1-6 in C57L mice was significantly promoted by the exosomal PDL1, which might be caused by the inhibitory effect of exosomal PDL1 on CD8⁺ T cells. Thus, exosomal PDL1 promotes the development and progression of HCC through inhibiting the anticancer activity of CD8⁺ T cells. This study provides sights for understanding the oncogenic role of PDL1 and a reasonable explanation for the low efficacy of anti-PD1/PDL1 immunotherapies in HCC.