Dissecting the Distinct Tumor Microenvironments of HRD and HRP Ovarian Cancer: Implications for Targeted Therapies to Overcome PARPi Resistance in HRD Tumors and Refractoriness in HRP Tumors.

ABSTRACT: High-grade serous tubo-ovarian cancer (HGSTOC) is an aggressive gynecological malignancy including homologous recombination deficient (HRD) and homologous recombination proficient (HRP) groups. Despite the therapeutic potential of poly (ADP-ribose) polymerase inhibitors (PARPis) and anti-PDCD1 antibodies, acquired resistance in HRD and suboptimal response in HRP patients necessitate more precise treatment. Herein, single-cell RNA and single-cell T-cell receptor sequencing on 5 HRD and 3 HRP tumors are performed to decipher the heterogeneous tumor immune microenvironment (TIME), along with multiplex immunohistochemistry staining and animal experiments for validation. HRD tumors are enriched with immunogenic epithelial cells, FGFR1+PDGFRβ+ myCAFs, M1 macrophages, tumor reactive CD8+/CD4+ Tre

SUBMITTER: Qiu J 

PROVIDER: S-EPMC11481286 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature