Biomolecules
The Antigen-Presentation Bottleneck in Pediatric Solid Tumors: Developmental Antigens, MHC-I Suppression, and Therapeutic Restoration of Tumor Immune Recognition
By Alghoul WII, Qassim ZAM, Neyyappadath RJ and 4 others.
Abstract
Background
Pediatric solid tumors respond poorly to T-cell-directed immunotherapy despite expressing developmentally restricted, cancer-testis, fusion-derived, and lineage-associated antigens, suggesting that therapeutic failure may reflect defective conversion of intracellular antigen expression into surface peptide-major histocompatibility complex class I (pMHC-I) display. This review examines the antigen-presentation bottleneck as a framework for tumor immune invisibility and therapeutic resistance.
Methods
We conducted a narrative mechanistic synthesis of pediatric and translational evidence on antigen repertoires, MHC-I and antigen-processing machinery dysfunction, mechanisms of presentation loss, therapeutic restoration, pMHC-directed immunotherapy, and MHC-independent bypass strategies.