Tumor‐Derived Peptidoglycan Recognition Protein 2 Predicts Survival and Antitumor Immune Responses in Hepatocellular Carcinoma

• DOI: 10.1002/hep.30924
• Publication Date: 2019-09-03T19:56:34Z
• Authors: Zongyi Yang; Jia Feng; Li Xiao; Xi Chen; Yuanfei Yao; Yiqun Li; Yu Tang; Shuai Zhang; Min Lu; Yu Qian; Hongjin Wu; Ming Shi
• Keywords: 0303 health sciences; Carcinoma, Hepatocellular; T-Lymphocytes; Tumor Suppressor Proteins; Liver Neoplasms; Original Articles; DNA Methylation; Lymphocyte Activation; Prognosis; DNA Methyltransferase 3A; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Cell Line, Tumor; Biomarkers, Tumor; Humans; Immunotherapy; Carrier Proteins; Promoter Regions, Genetic; Chemokine CCL5; Immunologic Surveillance

Background and Aims Hepatocellular carcinoma (HCC) is linked to immunosuppression. Relieving immunosuppression has been an attractive strategy improve the efficacy of cancer immunotherapy. Peptidoglycan recognition protein 2 (PGLYRP2) a pattern receptor which specifically expressed in liver implicated regulation innate immunity immunosurveillance. However, role hepatic PGLYRP2 modulating immune responses against HCC remains be investigated. Approach Results In this study, we investigated whether able influence progression through regulating host antitumor responses. We demonstrated that was down‐regulated HCC, with poor prognosis patients ( P < 0.001). overexpression cells significantly enhanced immune‐competent mice elevated response rates peripheral blood mononuclear . Mechanistically, DNA methyltransferase 3A–mediated promoter hypermethylation responsible for down‐regulation HCC. promoted production chemokine (C‐C motif) ligand 5 (CCL5) binding CCL5 promoter, contributed immunity. Conclusions provide evidence tumor‐derived acts as candidate biomarker adequate improved patient outcomes, indicating importance immunosurveillance designing immunotherapeutic approaches.