PTPN3 inhibition contributes to the activation of the dendritic cell function to augment the effect of cancer immunotherapy

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 therapeutic target for cancer immunotherapy was anticipated. However, evaluation of dendritic cell (DC) function as antigen-presenting cells is critical for development of immunotherapy. This study aimed to analyze the biological effect of PTPN3 on DCs induced from human peripheral blood monocytes obtained from healthy individuals. PTPN3 knockdown by siRNA significantly increased the number of DCs, the expression of CD80 and CCR7, and the production of IL-12p40/p70 in mature DCs. Using an HLA-A24-restricted DC and human lung squamous cell carcinoma cell cytotoxic assay, PTPN3 inhibition in mature DCs induced cytotoxic T lymphocytes with increased production of INF-γ and granzyme B and enhanced cytotoxicity against cancer cells and migration to cancer. Furthermore, PTPN3 inhibition activated the MAPK pathway in DCs. These findings suggest that PTPN3 inhibition can contribute to the development of novel cancer immunotherapies that not only activate lymphocytes, as previously reported, but also activate DCs.