CTLA4 and hepatocellular carcinoma: This is in line with a previous study showing that hepatocellular carcinoma (HCC)-derived exosome containing miR-146a enhance M2 macrophage polarization and consequently promote T-cell exhaustion by increasing Programmed cell Death protein 1 (PD-1), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and cytotoxic T-lymphocyte antigen 4 (CTLA4) expression (67) and suppress CD8+ T-cell activity by enhancing TIM-1+ Breg cells, consequently accelerating tumor development (68).