PTPN2 inhibitor 9 (PTP9) is small molecule inhibitor of protein tyrosine phosphatase non-receptor type 2 (PTPN2), sensitizes tumor cells to IFNγ treatment in vitro and to anti-PD-1 therapy in vivo.
PTP9 significantly upregulated both Cxcl11 and Ccl5 under the IFNγ stimulation condition in IFNγ and TNFα-treated B16F10 cells. PTP9 PTP9 mimicked Ptpn2 knockout phenotype in sensitizing B16F10 cells to IFNγ treatment in vitro.
PTP9 suppressed B16F10 cell growth and enhanced Stat1 phosphorylation and expression of IFNγ response genes.
PTP9 effectively sensitized B16F10 melanoma to ICI therapy in vivo, by restoring the ability to respond to IFNγ, thereby increasing T-cell chemokine expression and recruitment of cytolytic T cells to the tumor microenvironment.
PTP9 sensitized cancer cells to the effects of IFNγ and TNFα are not restricted to melanoma cells but extend to other solid tumors, many of which exhibit resistance to ICI therapy.