Protein tyrosine phosphatase non-receptor type 1 (PTPN1), a member of the protein tyrosine phosphatase superfamily, has been identified as an oncogene and therapeutic target in various cancers. However, its precise role in determining human cancer prognosis and immune response remains unclear. Here, a pan-cancer analysis shows that PTPN1 is highly expressed in multiple cancers. High PTPN1 expression is associated with poor prognosis in most cancers. Furthermore, PTPN1 expression is highly correlated with the presence of tumor-infiltrating immune cells and the expression of immune checkpoint pathway marker genes in different cancers. Moreover, PTPN1 can significantly predict the prognosis of patients receiving immunotherapy. CCK-8 cell viability assays showed that knocking down PTPN1 increased the sensitivity of MDA-MB-231 and MCF-7 cells to paclitaxel. Finally, the results indicate that PTPN1 is associated with immune infiltration and immune checkpoint gene expression in breast cancer.
To further validate the role of PTPN1 in the immune microenvironment of breast cancer, researchers constructed PTPN1 knockdown 4T1 breast cancer cells (Figure 1A). Next, they conducted in vivo mouse tumorigenesis experiments using a stably knockdown PTPN1 cell line. The results showed that tumors formed by PTPN1 knockdown cells were significantly smaller than those formed by control cells (Figure 1B and C). Furthermore, they performed immunofluorescence staining experiments to analyze the correlation between PTPN1 expression and tumor-associated macrophages (TAMs), CD8+ T cell infiltration, and PD-L1 expression in tumors derived from PTPN1 knockdown cells. PTPN1 deficiency significantly reduced the proportion of CD163+ M2-like TAMs (Figure 1D and E). Compared with tumors derived from control vector cells, CD8+ T cell infiltration was significantly reduced in tumors derived from PTPN1 knockdown cells (Figure 1F and G). In addition, researchers observed a positive correlation between PTPN1 expression and PD-L1 protein expression (Figure 1F and H). In summary, these results indicate that PTPN1 is associated with immune infiltration and immune checkpoint gene expression.
Figure 1. PTPN1 expression correlated with tumor growth and tumor immune infiltration in vivo. (Zhao R, et al., 2023)