Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Cell Immunol. 2020 Dec;358:104237. doi: 10.1016/j.cellimm.2020.104237. Epub 2020 Oct 17.
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.
我们之前报道过，在活化的淋巴细胞中上调的蛋白酪氨酸磷酸酶非受体型 3（PTPN3）可作为免疫检查点。然而，在活化的淋巴细胞中 PTPN3 表达增强的机制尚不清楚。在这项研究中，我们分析了活化的淋巴细胞中 PTPN3 表达的机制，以期开发一种抑制 PTPN3 的新型免疫检查点抑制剂。通过激活过程，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 在肿瘤微环境中降低了 PTPN3 的表达和 NFκB 的激活，并抑制了淋巴细胞的生物学活性。这项研究的结果有望为改善现有免疫疗法和开发新型免疫疗法提供重要意义。
