Structural Determinants and Repair of Membrane Microdomains in Dendritic Cell-Mediated Antitumor Immunity: An Integrative Mechanistic Synthesis

Durable responses to cancer immunotherapy remain restricted to a subset of patients, highlighting persistent gaps in understanding immune failure mechanisms. Dendritic cells (DCs) serve as the critical bridge between antigen recognition and adaptive im-mune activation, yet conventional molecular models centered on discrete components fail to fully explain heterogeneous therapeutic outcomes. This integrative mechanistic synthesis proposes that DC-mediated antitumor immun-ity is governed by higher-order structural determinants, including membrane micro-domain organization, spatial compartmentalization of signaling, and temporal inte-gration of antigenic and co-stimulatory cues. These features determine whether anti-gen presentation leads to effective T-cell priming or dysfunctional states such as ex-haustion or anergy within the tumor microenvironment. By reanalyzing our validated 2025 experimental pipeline alongside high-impact con-textual literature, we identify emergent properties of immune competence that trans-cend linear molecular interactions. The resulting framework distinguishes structurally mediated failure modes from classical resistance paradigms, providing a coherent non-reductionist explanation for variability in immunotherapy efficacy. Membrane raft repair is positioned as a key enabling structural condition for effective immune integration, with direct relevance to translational and regulatory contexts involving non-pharmacodynamic platforms and NAM-aligned evaluation strategies. This work establishes a unified mechanistic foundation to guide future hypothe-sis-driven studies and clinical advancement of DC-based approaches.