PTPROt maintains T cell immunity in the microenvironment of hepatocellular carcinoma

摘要

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.