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Updated: Jul 19, 2025
Novel Protocol for Generating Physiologic Immunogenic Dendritic Cells
Published on: May 17, 2019
PTPN3 inhibition contributes to the activation of the dendritic cell function to be a promising new immunotherapy
Naoya Iwamoto1, Hideya Onishi2, Shogo Masuda1
1Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
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.
Insights
Inhibiting protein tyrosine phosphatase non-receptor type 3 (PTPN3) enhances dendritic cell (DC) function, boosting anti-cancer immune responses. This finding supports PTPN3 as a target for novel cancer immunotherapies activating both lymphocytes and DCs.
Area of Science:
- Immunology
- Cancer Biology
- Cell Biology
Background:
- Protein tyrosine phosphatase non-receptor type 3 (PTPN3) was previously identified as an immune checkpoint molecule in lymphocytes.
- PTPN3's role in dendritic cell (DC) function, critical for immunotherapy development, remained largely unexplored.
Purpose of the Study:
- To investigate the biological effects of PTPN3 on human peripheral blood monocyte-derived dendritic cells (DCs).
- To assess the potential of targeting PTPN3 for enhancing DC-mediated anti-cancer immunity.
Main Methods:
- Short-interfering RNA (siRNA) was used to knockdown PTPN3 expression in DCs.
- DC maturation was induced using cancer cell lysate and TNF-α/IFN-α.
- Cytotoxic assays were performed using matched and unmatched cancer cell lines.
- Cytokine production and intracellular signaling pathways were analyzed via ELISA and intracellular staining.
Main Results:
- PTPN3 knockdown significantly increased DC numbers, CD80 and CCR7 expression, and IL-12 production.
- Inhibition of PTPN3 in mature DCs enhanced cytotoxic T lymphocyte induction, INF-γ and granzyme B production, and anti-cancer cell toxicity.
- PTPN3 inhibition promoted DC migration to cancer cells and activated the MAPK signaling pathway.
Conclusions:
- PTPN3 inhibition enhances DC maturation, function, and anti-tumor activity.
- Targeting PTPN3 represents a promising strategy for developing novel cancer immunotherapies that activate both DCs and lymphocytes.
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