Tumor-derived PD1 and PD-L1 could promote hepatocellular carcinoma growth through autophagy induction in vitro

Abstract

BackgroundsAutophagy in tumor was also found to influence immune microenvironment. The relation between autophagy and cancer intrinsic PD1 and PD-L1 expression was not clear. MethodsWith data from TCGA and GTEx databases, mRNA expression levels of autophagy-related genes were compared between tumor samples and normal tissues, which were also correlated with survival status. Expression of autophagy-related genes were also associated with clinical traits in datasets of GSE14520 and ICGC LIRI. Single sample gene set enrichment analysis (ssGSEA) was used to calculate autophagy scores in tumor samples, using signatures from MSigDB database. Lentivirus (PD1 and PD-L1), siRNA (ATG13) and plasmids (LC3A/B) were used to target specific genes in tumor cells; Western blot was used to examine protein expression accordingly. Co-immunoprecipitation was performed to find PD1 or PD-L1 interacting proteins; colony formation and EdU analysis were used to evaluate tumor cell growth abilities. ResultsmRNA levels of autophagy markers were increased in tumor and correlated with worse survival of cancer patients. In hepatocellular carcinoma (HCC), high mRNA expression of autophagy markers was related to poor clinical status; increasing LC3 expression in HCC cell lines could promote tumor growth. Tumor intrinsic PD1 or PD-L1 were related to higher autophagy levels in specific tumor types; over-expression of PD1 or PD-L1 could increase autophagy in tumor cells through ATG13 interaction. ConclusionAutophagy could promote tumor growth in specific cancer types. Tumor intrinsic PD1 or PD-L1 could both increase autophagy through ATG13 interaction.