Reprogramming the tumor immune microenvironment in cervical cancer: synergy between radiotherapy and immunotherapy.

Cervical cancer remains a major global health burden largely driven by persistent infection with high-risk human papillomavirus. Although immune-based therapies have transformed outcomes in several solid tumors, their benefit in cervical cancer has been modest, highlighting the need to understand and therapeutically exploit the tumor immune microenvironment. This review synthesizes current mechanistic and clinical evidence on viral-driven immunology, immune heterogeneity, and the bidirectional effects of radiotherapy on systemic and intratumoral immunity. We examine how radiation dose, fractionation, treatment volumes and temporal sequencing influence antigen release, innate sensing, T cell priming and trafficking, as well as detrimental consequences including lymphocyte depletion, checkpoint induction, expansion of suppressive myeloid and regulatory populations and stromal remodeling. Building on these insights, we discuss synergistic strategies to reprogram the tumor immune microenvironment, including combinations of radiotherapy with immune checkpoint inhibition, spatially informed field design that preserves anti-tumor immunity while limiting collateral lymphodepletion and adaptive response-guided treatment. We also highlight candidate biomarkers such as viral antigens, interferon pathway activation, T-cell clonality and spatial immune architecture that may enable patient selection, real-time treatment adaptation, and early detection of resistance. Converging preclinical and clinical data support a biomarker informed integration of radiotherapy and immunotherapy to overcome therapeutic resistance and to advance precision immuno-oncology in cervical cancer.