PTPN3 expressed in activated T lymphocytes is a candidate for a non-antibody-type immune checkpoint inhibitor

Akiko Fujimura, Kazunori Nakayama, Akira Imaizumi, Makoto Kawamoto, Yasuhiro Oyama, Shu Ichimiya, Masayo Umebayashi, Norihiro Koya, Takashi Morisaki, Takashi Nakagawa, Hideya Onishi

Research output: Contribution to journalArticle

Abstract

It has been shown that protein tyrosine phosphatase non-receptor type (PTPN) 3 inhibits T-cell activation. However, there is no definitive conclusion about how the inhibition of PTPN3 in lymphocytes affects immune functions in human lymphocytes. In the present study, we showed that PTPN3 inhibition significantly contributes to the enhanced activation of activated human lymphocytes. The PTPN3 expression of lymphocytes was significantly increased through the activation process using IL-2 and anti-CD3 mAb. Interestingly, inhibiting the PTPN3 expression in activated lymphocytes significantly augmented the proliferation, migration, and cytotoxicity through the phosphorylation of zeta-chain-associated protein kinase 70 (ZAP-70), lymphocyte-specific protein tyrosine kinase (LCK), and extracellular signal-regulated kinases (ERK). Lymphocyte activation by PTPN3 inhibition was observed only in activated CD3+ T cells and not in NK cells or resting T cells. In therapy experiments using autologous tumors and lymphocytes, PTPN3 inhibition significantly augmented the number of tumor-infiltrated lymphocytes and the cytotoxicity of activated lymphocytes. Our results strongly imply that PTPN3 acts as an immune checkpoint in activated lymphocytes and that PTPN3 inhibitor may be a new non-antibody-type immune checkpoint inhibitor for cancer therapy.

Original languageEnglish
Pages (from-to)1649-1660
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume68
Issue number10
DOIs
Publication statusPublished - Oct 1 2019

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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  • Cite this

    Fujimura, A., Nakayama, K., Imaizumi, A., Kawamoto, M., Oyama, Y., Ichimiya, S., Umebayashi, M., Koya, N., Morisaki, T., Nakagawa, T., & Onishi, H. (2019). PTPN3 expressed in activated T lymphocytes is a candidate for a non-antibody-type immune checkpoint inhibitor. Cancer Immunology, Immunotherapy, 68(10), 1649-1660. https://doi.org/10.1007/s00262-019-02403-y