PTPN3 expressed in activated T lymphocytes is a candidate for a non-antibody-type immune checkpoint inhibitor

PTPN3 is a potential target for a new cancer immunotherapy that has a dual effect of T cell activation and direct cancer inhibition in lung neuroendocrine tumor

“…A previous study reported that the cytotoxicity of PTPN3-suppressed activated lymphocytes was significantly enhanced compared with that of control activated lymphocytes [4] . To investigate the potential treatment strategy for PTPN3 inhibition in cancer patients, we performed an experiment using PTPN3-suppressed allo activated lymphocytes and examined the effects on cancer cells with suppression of PTPN3 ( Fig.…”

“…We previously showed that PTPN3 plays a pivotal role as an immune-checkpoint in activated lymphocytes [4] . Therefore, to explore the potential of PTPN3-targeting systemic treatment, we assessed the biological significance of PTPN3 in cancer cells in the presence of PTPN3-suppressed allo or autocrine activated lymphocytes ( Fig.…”

“…Control shRNA–expressing lymphocytes was performed in the same manner, and target and effector cells were co-incubated for 48 h [Effector cells (activated lymphocytes) at an effector/target (E/T) ratio of 20:1 were added to the culture]. Lymphocytes that we used mainly consist of CD3 + activated T cells [4] . To quantify viable adherent cancer cells, Cell Count Reagent SF was added to the washed wells, followed by incubation for 1 h at 37C.…”

“…Immune checkpoint inhibitors have recently attracted attention as a new cancer treatment due to their remarkable efficacy [1] , [2] , [3] . We previously showed that protein tyrosine phosphatase non-receptor type3 (PTPN3), which is upregulated in activated lymphocytes, is a novel immune checkpoint molecule that regulates lymphocyte activation [4] . PTPN3 inhibitors have the potential to be orally administered and appear to be a very promising drug for cancer treatment.…”

“…Upon stimulation of the TCR/CD3 complex in lymphocytes, phosphorylation of Lck and Zap70 is enhanced and the MAPK pathway is activated, resulting in lymphocyte proliferation and hyperfunction. This mechanism increases the expression of PTPN3, which suppresses lymphocyte activation [4] . Several studies have shown that PTPN3 enhances the malignant traits of various cancers.…”