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Journal of Cancer Research and Clinical Oncology

Erschienen in:

16.08.2023 | Research

PTPN3 inhibition contributes to the activation of the dendritic cell function to be a promising new immunotherapy target

verfasst von: Naoya Iwamoto, Hideya Onishi, Shogo Masuda, Akira Imaizumi, Keita Sakanashi, Shinji Morisaki, Shinjiro Nagao, Satoko Koga, Keigo Ozono, Masayo Umebayashi, Takashi Morisaki, Masafumi Nakamura

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 16/2023

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Abstract

Purpose

In a previous study, protein tyrosine phosphatase non-receptor type (PTPN) 3 was identified as an immune checkpoint molecule in lymphocytes, and its potential as a novel target for cancer immunotherapy was anticipated. However, evaluation of dendritic cell (DC) function as antigen-presenting cells is critical for the development of immunotherapy. In this study, we aimed to analyze the biological effect of PTPN3 on DCs induced from human peripheral blood monocytes obtained from healthy individuals.

Methods

We used short-interfering RNA to knock down PTP3 in DCs. For DC maturation, we added cancer cell lysate and tumor necrosis factor-α/interferon-α to immature DCs. In the cytotoxic assay, the target cancer cells were SBC5, unmatched with DCs from healthy human leukocyte antigen (HLA)-A24, or Sq-1, matched with DCs. Enzyme-linked immunosorbent assay was used to determine the amount of cytokines. To examine the intracellular signaling system, intracellular staining was used.

Results

PTPN3 knockdown significantly increased the number of DCs, expression of CD80 and chemokine receptor (CCR)7, and production of interleukin-12p40/p70 in mature DCs. In the HLA-A24-restricted DC and human lung squamous cell carcinoma cell cytotoxic assay, inhibition of PTPN3 expression in mature DCs induced cytotoxic T lymphocytes with increased production of INF-γ and granzyme B, and enhanced toxicity against cancer cells and migration to cancer. Furthermore, inhibition of PTPN3 expression activated the mitogen-activated protein kinase pathway in DCs.

Conclusion

Based on our findings, inhibition of PTPN3 expression could contribute to the development of novel cancer immunotherapies that activate not only lymphocytes but also DCs.

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Titel: PTPN3 inhibition contributes to the activation of the dendritic cell function to be a promising new immunotherapy target
verfasst von: Naoya Iwamoto
Hideya Onishi
Shogo Masuda
Akira Imaizumi
Keita Sakanashi
Shinji Morisaki
Shinjiro Nagao
Satoko Koga
Keigo Ozono
Masayo Umebayashi
Takashi Morisaki
Masafumi Nakamura
Publikationsdatum: 16.08.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 16/2023
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-023-05250-8

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PTPN3 inhibition contributes to the activation of the dendritic cell function to be a promising new immunotherapy target