Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits profound resistance to immunotherapy due to its highly immunosuppressive tumor microenvironment (TME). Objective: This review aims to elucidate the key mechanisms of TME-mediated immune evasion in PDAC and explore therapeutic strategies to overcome these barriers. Methods: A comprehensive analysis of recent studies was conducted, focusing on the cellular, stromal, and metabolic components of the PDAC TME, alongside emerging technologies for TME reprogramming. Results: Dense extracellular matrix, CAF-driven fibrosis, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), Tregs, and metabolic competition collectively impair immune cell infiltration and activation. Novel interventions-including ECM remodeling, CAF modulation, metabolic reprogramming, and myeloid cell targeting-show promise in restoring immune responsiveness. Conclusion: TME reprogramming represents a critical strategy to enhance immunotherapy efficacy in PDAC, offering new opportunities for overcoming immune exclusion and resistance.
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Hui et al. (2025) studied this question.
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