卵巢癌双重微环境免疫逃逸机制与靶向策略OA

Epithelial ovarian cancer(EOC),particularly high-grade serous ovarian cancer(HGSOC),commonly presents with intraperitoneal dissemination,peritoneal implants,and malignant ascites.The objective response rate to immune checkpoint inhibitor(ICI)monotherapy is approximately 8％-15％.A key underlying reason is that the distinctive intraperitoneal spread of EOC places tumor cells simultaneously within both a"solid"microenvironment(formed by solid lesions/peritoneal implants)and a"liquid"microenvironment(represented by malignant ascites);these two compartments continuously interact through cellular trafficking,exosome-mediated transfer,cytokine diffusion,and lipid metabolic exchange,collectively shaping the typical"cold tumor"phenotype.Centered on this solid-liquid dual microenvironment,this review dissects,at the cellular level,the immunosuppressive network established by M2-polarized tumor-associated macrophages,enriched regulatory T cells,expanded myeloid-derived suppressor cells,and dysfunctional dendritic/NK and CD8+T cells;and elucidates,at the molecular level,the central roles of IL-4/IL-6/TGF-β/VEGF cytokine axis imbalance,lipid metabolic reprogramming,lactate accumulation,and impaired antigen presentation in driving T-cell exhaustion and platinum resistance.On the therapeutic front,integrating the latest evidence from KEYNOTE-B96,DUO-O,FIRST/ENGOT-OV44,ATHENA-COMBO,MIRASOL,OVHIPEC-1 and PIPAC studies,this review summarizes the evidence supporting immune-combination regimens,anti-angiogenic agents,folate receptor alpha antibody-drug conjugates,hyperthermic intraperitoneal chemotherapy,and local intraperitoneal delivery from the dual perspectives of systemic immune modulation and local microenvironment intervention.The dual-microenvironment framework may help explain the poor response to immunotherapy and inform rational combination strategies in EOC;however,clinical translation should be based on precise stratification according to histology,BRCA/homologous recombination deficiency status,PD-L1 and folate receptor alpha expression,and spatial immune phenotypes.