PTPN3 inhibition contributes to the activation of the dendritic cell function to be a promising new immunotherapy target.
Anticancer immunotherapy
Immune checkpoint
MAPK pathway
Mature dendritic cell
PTPN3
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
24
06
2023
accepted:
04
08
2023
medline:
27
10
2023
pubmed:
16
8
2023
entrez:
16
8
2023
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 37584709
doi: 10.1007/s00432-023-05250-8
pii: 10.1007/s00432-023-05250-8
doi:
Substances chimiques
Cytokines
0
Interleukins
0
PTPN3 protein, human
EC 3.1.3.48
Protein Tyrosine Phosphatase, Non-Receptor Type 3
EC 3.1.3.48
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
14619-14630Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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