Neoadjuvant chemotherapy reduces regulatory T-cells in cervical cancer.

BACKGROUND: The tumor microenvironment (TME) in cervical cancer may undergo immunological changes during neoadjuvant chemotherapy (NACT). The primary aim of this study was to elucidate changes in the TME of cervical cancer during platinum-containing NACT and to evaluate whether these immunological changes correlated with survival. Characterizing these changes may help identify the optimal timing for future integration of immunotherapy. This study examined alterations in lymphocyte subsets in patients with FIGO 2009 stage IB2-IIA2 cervical cancer treated with cisplatin-based NACT. METHODS: Tissue samples from 64 patients enrolled in EORTC trial 55994 were analyzed. Baseline biopsies (n = 55) and post-NACT surgical specimens (n = 43) underwent multiplex immunohistochemistry with fluorescent labels to quantify B cells, CD8 and helper T-cells, regulatory T-cells (Tregs), and tumor cells. Proliferation was assessed using Ki67 expression. ImmuNet, a validated machine-learning-based image analysis platform, was used for cell identification and density measurements. FINDINGS: Following NACT, Treg density significantly decreased in stromal (p < 0.0001) and intratumoral regions (p = 0.0007). A lower proportion of proliferating Tregs after treatment was associated with better OS (p = 0.018). Changes in other lymphocyte subsets were less consistent. INTERPRETATION: NACT appears to reduce Treg-mediated immunosuppression in the cervical cancer TME. Patients with low post-treatment Treg proliferation demonstrated more favourable survival. These findings are hypothesis-generating and suggest that the immune microenvironment following NACT warrants further investigation, including studies evaluating the optimal timing of immunotherapy.