We previously reported that protein tyrosine phosphatase non-receptor type 3 (PTPN3), which is upregulated in activated lymphocytes, acts as an immune checkpoint. However, the mechanism by which PTPN3 expression is enhanced in activated lymphocytes is unknown. In this study, we analyzed the mechanism of PTPN3 expression in activated lymphocytes with a view for developing a novel immune checkpoint inhibitor that suppresses PTPN3. Through the activation process, lymphocytes showed enhanced NFκB activation as well as increased PTPN3 expression. NFκB enhanced proliferation, migration, and cytotoxicity of lymphocytes. Furthermore, NFκB enhanced PTPN3 expression and tyrosine kinase activation. TGFβ reduced PTPN3 expression and NFκB activation in the cancer microenvironment, and suppressed the biological activity of lymphocytes. The results of this study are expected to provide significant implications for improving existing immunotherapy and developing novel immunotherapy.

我们以前曾报道过，在活化的淋巴细胞中上调的蛋白酪氨酸磷酸酶非受体3型（PTPN3）充当免疫检查点。但是，激活的淋巴细胞中增强PTPN3表达的机制尚不清楚。在这项研究中，我们分析了激活的淋巴细胞中PTPN3表达的机制，以期开发出一种抑制PTPN3的新型免疫检查点抑制剂。在激活过程中，淋巴细胞显示出增强的NFκB激活以及增加的PTPN3表达。NFκB增强了淋巴细胞的增殖，迁移和细胞毒性。此外，NFκB增强了PTPN3的表达和酪氨酸激酶的激活。TGFβ降低了癌症微环境中PTPN3的表达和NFκB的活化，并抑制了淋巴细胞的生物学活性。