Mechanisms of Immune Evasion in the Dual Tumor Microenvironment of Ovarian Cancer and Targeted Therapeutic Strategies
10.11714/jsysu.med.YX20260120
- VernacularTitle:卵巢癌双重微环境免疫逃逸机制与靶向策略
- Author:
Karima ABDUGHENI·
1
;
Junxiu LIU
1
Author Information
1. Department of Obstetrics and Gynecology， The First Affiliated Hospital， Sun Yat-sen University， Guangzhou 510080， China
- Publication Type:Review
- Keywords:
ovarian cancer;
tumor microenvironment;
ascites;
immune evasion;
immune checkpoint inhibitors
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2026;47(5):767-779
- CountryChina
- Language:Chinese
-
Abstract:
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.
