Figure 2.
Role of exosomes in the inhibitory adaptive immune microenvironment in HCC. (A) HCC secrete PCED1B-AS1, 14-3-3ζ rich exosomes to inhibit the function of CD8+ T lymphocytes directly. (B) HCC transmitted overexpressed circTMEM181 to macrophages through exosomes, leading to the enrichment of adenosine in the TIME and thereby damaging the function of CD8+ T cells. (C) Exosomes containing circTMEM181, miR-23a-3p, miR-146a-5p secreted by HCC promote M2 macrophage polarization, thus impairs the CD8+ T cells. (D) HMGB1 mRNA promotes the production of PD-L1-rich exosomes, exosomes transport PD-L1 to macrophages and other HCC cells. PD-L1 on the surface of tumor-derived exosomes and cells interact with PD-1 on the surface of CD8+ T cells to induce apoptosis, exhaustion, and inactivation of CD8+ T cells. (E–G) HCC–derived exosomes increased Breg, Treg and Th17 expression via many mechanisms and mediated the imbalance of Th17/Treg.