Targeting LxCxE Cleft Pocket of Retinoblastoma Protein in Immunosuppressive Macrophages Inhibits Ovarian Cancer Progression.

ABSTRACT: Ovarian cancer remains a major health threat with limited treatment options available. It is characterized by an immunosuppressive tumor microenvironment (TME) maintained by tumor-associated macrophages (TAM), hindering antitumor responses and immunotherapy efficacy. In this study, we showed that targeting retinoblastoma protein (Rb) by disruption of its LxCxE cleft pocket caused preferential cell death in Rbhigh M2-polarized or M2-like Rbhigh immunosuppressive TAMs by induction of endoplasmic reticulum stress, p53, and mitochondria-related cell death pathways. A reduction of protumor immunosuppressive macrophages from TME in vivo resulted in enhanced T-cell infiltration and T-cell antitumor response and inhibited cancer progression. We demonstrated increased Rb expression in TAMs in women

SUBMITTER: Tcyganov EN 

PROVIDER: S-EPMC12532034 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature