Small-molecule PTPN2 Inhibitors Sensitize Resistant Melanoma to Anti-PD-1 Immunotherapy.

ABSTRACT: Although immune checkpoint inhibitors targeting T-cell immunoregulatory proteins have revolutionized cancer treatment, they are effective only in a limited number of patients, and new strategies are needed to enhance tumor responses to immunotherapies. Deletion of protein tyrosine phosphatase non-receptor type 2 (Ptpn2), a regulator of growth factor and cytokine signaling pathways, has been shown to sensitize murine B16F10 melanoma cells to IFNγ and anti-PD-1 immunotherapy. Here, we investigated the potential therapeutic utility of small-molecule PTPN2 inhibitors. Ten inhibitors were synthesized on the basis of in silico modeling and structure-based design and functionally tested in vitro and in vivo. We show that the inhibitors had little effect on B16F10 cells alone,

SUBMITTER: Zhu Z 

PROVIDER: S-EPMC10035454 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature