Human T-Lymphotropic Virus Type 1 (HTLV-1): Molecular Markers, Immunopathogenesis and Future Perspectives for Vaccine Development and Immunotherapy in Adult T-Cell Leukemia/ Lymphoma

Background: Human T-lymphotropic virus type 1 (HTLV-1) is a complex oncogenic delta-retrovirus and the causative agent of Adult T-cell Leukemia/Lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).Infecting an estimated 5-10 million individuals globally, the virus exerts its oncogenic potential through two pivotal regulatory proteins: Tax and the HTLV-1 basic leucine zipper factor (HBZ), which orchestrate a cascade of molecular events including NF-κB activation, epigenetic reprogramming, immune evasion and clonal T-cell expansion.Despite decades of research, no prophylactic or therapeutic vaccine has received clinical approval.Objectives: This review comprehensively synthesizes current knowledge on HTLV-1 molecular pathogenesis, key molecular biomarkers, HLA-restriction of immune responses and emerging vaccine strategies including peptide-based, DNA-based, mRNA-based, viral vector and dendritic cell-based platforms.It further explores the therapeutic landscape of ATLL including mogamulizumab (anti-CCR4), CAR-T cell therapy and checkpoint inhibitors.Methods: A systematic narrative review of literature from PubMed, Scopus and Web of Science was performed, incorporating 50 peer-reviewed references spanning foundational discoveries to recent clinical trials as of 2024.Conclusion: The molecular complexity of HTLV-1 -particularly the dichotomous roles of Tax and HBZ, HLA-restricted CTL immunodominance and proviral load as a prognostic biomarker -offers multiple actionable targets for next-generation vaccine and immunotherapy design.Integrating multi-epitope mRNA platforms, HBZ-directed CTL induction and combination immunotherapy holds transformative promise for this neglected yet lethal retroviral malignancy.