Concurrent Chemoradiotherapy Plus Immunotherapy Versus Concurrent Chemoradiotherapy in Locally Advanced Cervical...

Concurrent chemoradiotherapy (CCRT) followed by intrauterine brachytherapy is the standard treatment for locally advanced cervical cancer (LACC), yet its efficacy is frequently constrained by an immunosuppressive tumor microenvironment (TME). This randomized, single-center, Phase II trial (n = 18; 2:1 allocation; high-risk Stages III-IVA LACC) investigated whether adding immunotherapy to CCRT (CICRT) could enhance early tumor regression and overcome immune suppression. In this exploratory analysis, CICRT demonstrated a numerical advantage in tumor reduction over CCRT alone, although the difference did not reach conventional statistical significance (mean residual tumor volume: 3.0% vs. 7.4%, p = 0.080, 95% CI: -9.3%-0.6%, η ² = 0.180). Single-cell RNA sequencing of paired biopsies (n = 12) revealed that CICRT was associated with pro-inflammatory remodeling, characterized by the upregulation of MHC-II and chemotaxis-related genes in malignant cells and cancer-associated fibroblasts. Notably, CICRT reduced regulatory T cell niches and exhausted CD8⁺ T cells, alongside a phenotypic shift in tumor-associated macrophages toward an inflammatory state. These findings demonstrate the potential of CICRT to enhance early tumor regression and mitigate TME suppression, providing an exploratory biological rationale for its therapeutic activity in LACC.