Dendritic cell fate plasticity: a central switch in the tumor immune landscape

Dendritic cells (DCs) are key antigen-presenting cells that initiate antitumor immunity, yet DCs in the tumor microenvironment (TME) are often functionally impaired. Unlike previous reviews that focus on DC dysfunction, this review argues that the main effect of the TME on DCs is not passive dysfunction but active fate hijacking. Through this hijacking, DC populations and states are shifted from antitumor sentinels toward immunosuppressive accomplices. This review follows a causal chain from fate determination, through fate deviation, to fate reprogramming. It first describes how the lineage fate of DC subsets is determined by transcription factor networks. It then summarizes how the TME hijacks DC fate through hierarchical mechanisms, including metabolic deprivation, inhibitory signals, epigenetic remodeling, death evasion, and physical barriers. Two reprogramming strategies are discussed: direct DC modification and indirect niche remodeling. Finally, the review focuses on precision interventions that depend on tumor type and niche. This review systematically covers 129 publications from 2008 to 2026, including 90 original studies, 8 clinical studies, and 31 reviews. Together, this synthesis provides an actionable framework for DC-centered precision immunotherapy.