Cancer-associated fibroblasts and immune evasion in endometrial cancer: current evidence and therapeutic perspectives

Abstract

Cancer-associated fibroblasts (CAFs) are potential contributors to tumor progression and immune resistance in endometrial cancer (EC), but the extent of EC-specific mechanistic and therapeutic evidence remains uneven. Studies using EC-derived fibroblasts support tumor-promoting paracrine activity and provide experimental evidence of altered natural killer cell function. Single-cell and spatial analyses further characterize stromal heterogeneity and candidate intercellular interactions. However, many proposed mechanisms of CAF-mediated immune exclusion and most CAF-directed therapeutic strategies are informed by studies in other malignancies. This review distinguishes findings obtained in EC patient samples and experimental models from evidence extrapolated from pancreatic, breast, gastric, and other cancers. We examine CAF heterogeneity, soluble signaling, matrix remodeling, and immune-cell interactions, while identifying where functional validation in EC is still required. Therapeutic approaches, including FAP-directed interventions, stromal reprogramming, and signaling blockade combined with immune checkpoint inhibition, are discussed as candidate research strategies rather than established EC treatments. Priorities include validating CAF-immune mechanisms in EC, developing reproducible stromal biomarkers, and testing treatment combinations in appropriate disease-specific models and clinical studies.