Peripheral FOXP3+ regulatory T cells as potential predictive markers of concurrent chemoradiation therapy response in...

Concurrent chemoradiation therapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC); however, approximately 30% of patients respond poorly, and alternative therapeutic options remain limited. We aimed to identify peripheral immune biomarkers associated with treatment response and characterize the immune mechanisms underlying clinical outcomes. Thirty patients with LACC undergoing CCRT were enrolled and classified three months after treatment as responders (n = 15) or non-responders (n = 15) according to Response Evaluation Criteria in Solid Tumors. Peripheral blood mononuclear cells were collected at baseline and at one and three months after treatment. Flow cytometry was used to analyze CD4⁺ and CD8⁺ T cells, CD4⁺ forkhead box P3 (FOXP3)⁺ regulatory T cells, interferon gamma (IFN-γ)- and interleukin-10 (IL-10)-producing T cells, and programmed cell death protein 1 (PD-1)-expressing exhausted T cells. Responders showed elevated baseline levels of CD4⁺ T cells, FOXP3⁺ regulatory T cells, and IL-10-producing CD4⁺ T cells, together with increased IFN-γ-producing CD8⁺ T cells during treatment. Non-responders exhibited elevated PD-1-expressing CD8⁺ T cells and reduced regulatory and effector T-cell activity. Ratios incorporating FOXP3⁺ regulatory T cells and PD-1 expression demonstrated strong predictive performance, with area under the curve values up to 0.98. These findings indicate that a balanced regulatory-to-effector T-cell profile is associated with favorable response to CCRT, whereas increased T-cell exhaustion is linked to treatment failure. Peripheral immune profiling may provide a minimally invasive approach for early prediction of treatment outcomes in LACC.