The tumor microenvironment: a dynamic ecosystem and therapeutic ...
www.frontiersin.org
June 28, 2026, 3:24 p.m.
The tumor microenvironment functions as a dynamic ecosystem that orchestrates carcinogenesis, therapeutic resistance, and immune evasion. This comprehensive review examines the cellular and acellular architecture of the TME, including cancer-associated fibroblasts, tumor-associated macrophages, and remodeled extracellular matrix. The authors analyze molecular mechanisms underlying TME-mediated pathogenesis, encompassing metabolic reprogramming, epigenetic dysregulation, and microbiome interactions that collectively drive immunosuppression. The review highlights emerging therapeutic strategies, including precision nanotechnologies, next-generation immunotherapies such as logic-gated CAR-T cells and bispecific engagers, metabolic modulators, stromal normalization, and microbiome interventions. Advanced tools including patient-derived organoids, tumor-on-a-chip systems, and artificial intelligence-powered multi-omics enable personalized therapeutic forecasting, offering transformative approaches to overcome intratumoral heterogeneity and therapeutic challenges.