PTPN1/PTPN2 inhibition improves NK cancer therapy by enhancing IL-2 and mitigating TGFβ1 responses

ABSTRACT: Natural killer (NK) cells are promising candidates for allogeneic anti-cancer immunotherapy. However, their cytolytic activity is often suppressed by the tumour microenvironment. We demonstrate that genetic silencing or pharmacological dual inhibition of protein tyrosine phosphatases PTPN1 and PTPN2 (PTPN1/N2) in NK cells significantly enhances anti-tumour cytolytic activity both in vitro and in vivo. This augmented NK cell activity is mediated by increased expression of early activation markers and the production of effector molecules such as granzyme B and interferon-gamma (IFN-γ). Notably, this elevated cell cytolytic response remains substantially resistant to the immunosuppressive effects of TGFβ-1, a cytokine known to dampen NK cell activity and commonly present in the tumour microen

SUBMITTER: Chu-Han Feng 

PROVIDER: S-SCDT-10_1038-S44319-026-00745-0 | biostudies-other |

REPOSITORIES: biostudies-other