在先前的研究中，已经确定了蛋白酪氨酸磷酸酶非受体型（PTPN）3是淋巴细胞中的免疫检查点分子，并且有望成为肿瘤免疫疗法的新靶点。然而，评估树突状细胞（DC）作为抗原呈递细胞的功能对于免疫疗法的发展至关重要。因此，本研究旨在分析PTPN3对从健康个体获得的人体外周血单核细胞诱导的DC的生物学效应。我们使用短干扰RNA沉默DC中的PTPN3。对于DC的成熟，我们加入癌细胞溶解液和肿瘤坏死因子-α/干扰素-α到未成熟的DC中。在细胞毒性试验中，目标癌细胞为SBC5，与健康人白细胞抗原（HLA）-A24不匹配的DC或与DC匹配的Sq-1。我们使用酶联免疫吸附测定法确定细胞因子的数量。为了检查细胞内信号传导系统，我们使用细胞内染色法。PTPN3沉默显著增加了DC的数量，CD80和趋化因子受体（CCR）7的表达，并增加了成熟DC的白细胞介素-12p40/p70的产生。在HLA-A24限制性DC和人肺鳞癌细胞细胞毒性试验中，PTPN3在成熟DC中的抑制诱导了产生增加的干扰素-γ和粒酶B的细胞毒性T淋巴细胞，增强了对癌细胞的毒力和对癌症的迁移。此外，PTPN3的抑制活化了DC中的丝裂原活化蛋白激酶信号通路。根据我们的发现，PTPN3的抑制有可能促进新的癌症免疫疗法的发展，不仅激活淋巴细胞，还激活DC。© 2023. 作者，独家许可给Springer-Verlag GmbH Germany，Springer Nature的一部分。

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.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.