Progress and challenges in PTPN1/PTPN2 regulation of tumor immune escape

Tumor Microenvironment (TME) refers to tumor cells and their microenvironment, which mainly consists of tumor cells and their surrounding immune and inflammatory cells, tumor-associated fibroblasts and nearby mesenchymal tissues, tumor vasculature, as well as a variety of cytokines and chemokines. TME affects tumor growth, metastatic spread, and therapeutic response, and plays an important role in tumorigenesis, metastasis as well as evasion of immune monitoring and treatment at all stages, and is a key and central issue in modern tumor biology. The core feature of TME is its immunosuppressive nature, and targeting PTPN1/2 enhances anti-tumor response by reversing immunosuppression. Whereas protein tyrosine phosphatases (PTPs) have long been recognized to play an important role in cancer cell biology and regulation of immune responses, PTPN1 (protein tyrosine phosphatase non-receptor type 1) and PTPN2 (protein tyrosine phosphatase non-receptor type 2), also known as TCPTP (T-cell protein tyrosine phosphatase) are both PTPs (protein tyrosine phosphatases) family. In this review, the mechanisms underlying the tumorigenic and tumor suppressor functions of non-receptor PTPs in tumor cells are summarized, and recent progress in the development of PTPN1/PTPN2 inhibitors as antitumor agents for tumor immunotherapy is discussed and described in relation to their effects on the tumor microenvironment.