PTPROt maintains T cell immunity in the microenvironment of hepatocellular carcinoma

J Mol Cell Biol. 2015 Aug;7(4):338-50. doi: 10.1093/jmcb/mjv047. Epub 2015 Jun 27.


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.

Keywords: PTPROt; Teff; Treg; hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / pathology
  • Cell Differentiation
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Humans
  • Immunity*
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / pathology
  • Lymphocyte Activation / immunology
  • Male
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Middle Aged
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / deficiency
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / metabolism*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Microenvironment / immunology*


  • PTPRO protein, human
  • Ptpro protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3