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 microenviron...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-typeO(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.展开更多
基金supported by grants from the National Natural Science Foundation for Distinguished Young Scholars(81225017 to B.S.)the State Key Program of National Natural Science of China(81430062 to B.S.)+3 种基金the National Basic Research Program of China(2012CB910800 to B.S.)the National Natural Science Foundation of China(81302106 to J.H.81201528 to R.J.)supported in part by the Priority Academic Program of Jiangsu Higher Education Institutions.
文摘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-typeO(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.
