Chen Zheng, Liu Shuang, Xie Peiyi, Zhang Bo, Yu Mincheng, Yan Jiuliang, Jin Lei, Zhang Wentao, Zhou Binghai, Li Xiaoqiang, Xiao Yongsheng, Xu Yongfeng, Ye Qinghai, Li Hui, Guo Lei
Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China.
Neurosurgery Department of Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.
Biochem Biophys Res Commun. 2022 May 21;605:82-89. doi: 10.1016/j.bbrc.2022.03.075. Epub 2022 Mar 17.
Autophagy in tumor was also found to influence immune microenvironment. The relation between autophagy and cancer intrinsic PD1 and PD-L1 expression was not clear.
With 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.
mRNA 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.
Autophagy could promote tumor growth in specific cancer types. Tumor intrinsic PD1 or PD-L1 could both increase autophagy through ATG13 interaction.
肿瘤中的自噬也被发现会影响免疫微环境。自噬与癌症内在的PD1和PD-L1表达之间的关系尚不清楚。
利用来自TCGA和GTEx数据库的数据，比较肿瘤样本与正常组织中自噬相关基因的mRNA表达水平，并将其与生存状态相关联。自噬相关基因的表达也与GSE14520和ICGC LIRI数据集中的临床特征相关。使用来自MSigDB数据库的特征，通过单样本基因集富集分析（ssGSEA）计算肿瘤样本中的自噬评分。使用慢病毒（PD1和PD-L1）、小干扰RNA（ATG13）和质粒（LC3A/B）靶向肿瘤细胞中的特定基因；相应地使用蛋白质免疫印迹法检测蛋白质表达。进行免疫共沉淀以寻找与PD1或PD-L1相互作用的蛋白质；使用集落形成和EdU分析评估肿瘤细胞的生长能力。
肿瘤中自噬标志物的mRNA水平升高，且与癌症患者较差的生存率相关。在肝细胞癌（HCC）中，自噬标志物的高mRNA表达与不良临床状态相关；在HCC细胞系中增加LC3表达可促进肿瘤生长。肿瘤内在的PD1或PD-L1与特定肿瘤类型中较高的自噬水平相关；PD1或PD-L1的过表达可通过与ATG13相互作用增加肿瘤细胞中的自噬。
自噬可在特定癌症类型中促进肿瘤生长。肿瘤内在的PD1或PD-L1均可通过与ATG13相互作用增加自噬。
