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: Jiajie Hou, Lei Deng, Han Zhuo, Zhe Lin, Yun Chen, Runqiu Jiang, Dianyu Chen, Xudong Zhang, Xingxu Huang, Beicheng Sun
• Journal: Journal of molecular cell biology (J Mol Cell Biol) Vol. 7 Issue 4 Pg. 338-50 (Aug 2015) ISSN: 1759-4685 [Electronic] United States
• PMID: 26117839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

Chemical References

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

Topics

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