title: PTPROt maintains T cell immunity in the microenvironment of hepatocellular carcinoma.
abstract: Intratumoral T cells play a central role in anti-tumor immunity, and the balance between T effector cells (Teff) and regulatory T cells (Treg) affects the prognosis of cancer patients. However, educated by tumor microenvironment, T cells frequently fail in their responsibility. In this study, we aimed to investigate the role of truncated isoform of protein tyrosine phosphatase receptor-type O (PTPROt) in T cell-mediated anti-tumor immunity. We recruited 70 hepatocellular carcinoma (HCC) patients and 30 healthy volunteers for clinical investigation, and analyzed cellular tumor immunity by using ptpro(-/-) C57BL/6 mice and NOD/SCID mice. PTPROt expression was significantly downregulated in human HCC-infiltrating T cells due to the hypoxia microenvironment; PTPROt expression highly correlated with the intratumoral Teff/Treg ratio and clinicopathologic characteristics. Moreover, PTPROt deficiency attenuated T cell-mediated anti-tumor immunity and remarkably promoted mouse HCC growth. Mechanistically, deletion of PTPROt decreased Teff quantity and quality through phosphorylation of lymphocyte-specific tyrosine kinase, but increased Treg differentiation through phosphorylation of signal transducer and activator of transcription 5. In support of the Teff/Treg homeostasis, PTPROt serves as an important tumor suppressor in HCC microenvironment.
authors.affiliation: Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China Present address: Liver Transplantation Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jiajie
authors.initials: J
authors.lastname: Hou
authors.affiliation: Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Deng
authors.affiliation: Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhuo
authors.affiliation: Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Runqiu
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Dianyu
authors.initials: D
authors.lastname: Chen
authors.affiliation: Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, China.
authors.forename: Xingxu
authors.initials: X
authors.lastname: Huang
authors.affiliation: Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China sunbc@njmu.edu.cn.
authors.forename: Beicheng
authors.initials: B
authors.lastname: Sun
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007109:Immunity; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008875:Middle Aged; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000172:deficiency / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: C516888:PTPRO protein, human; C516890:Ptpro protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3
keywords: PTPROt; Teff; Treg; hepatocellular carcinoma