NFκB and TGFβ contribute to the expression of PTPN3 in activated human lymphocytes

Cell Immunol. 2020 Dec:358:104237. doi: 10.1016/j.cellimm.2020.104237. Epub 2020 Oct 17.

Abstract

We previously reported that protein tyrosine phosphatase non-receptor type 3 (PTPN3), which is upregulated in activated lymphocytes, acts as an immune checkpoint. However, the mechanism by which PTPN3 expression is enhanced in activated lymphocytes is unknown. In this study, we analyzed the mechanism of PTPN3 expression in activated lymphocytes with a view for developing a novel immune checkpoint inhibitor that suppresses PTPN3. Through the activation process, lymphocytes showed enhanced NFκB activation as well as increased PTPN3 expression. NFκB enhanced proliferation, migration, and cytotoxicity of lymphocytes. Furthermore, NFκB enhanced PTPN3 expression and tyrosine kinase activation. TGFβ reduced PTPN3 expression and NFκB activation in the cancer microenvironment, and suppressed the biological activity of lymphocytes. The results of this study are expected to provide significant implications for improving existing immunotherapy and developing novel immunotherapy.

Keywords: Activated lymphocyte; Immunotherapy; NFκB; PTPN3; TGFβ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Humans
  • Lymphocyte Activation / immunology
  • Lymphocytes / metabolism
  • NF-kappa B / metabolism*
  • NF-kappa B / physiology
  • Phosphorylation / immunology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 3 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 3 / metabolism*
  • Signal Transduction / immunology
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / physiology

Substances

  • NF-kappa B
  • Transforming Growth Factor beta
  • PTPN3 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 3