The Dynamic alternation of Local and Systemic Tumor Immune Microenvironment during Concurrent Chemoradiotherapy of Cervical Cancer: A Prospective Clinical Trial
Abstract
PURPOSE
This work assessed local and systemic alternations of the tumor immune microenvironment (TIME) during concurrent chemoradiotherapy (CCRT) of local advanced cervical cancer to estimate the optimal timing for immune therapy in relation to CCRT.
METHODS
In this single-center prospective clinical trial, 55 patients with stage IIA-IVA cervical cancer were enrolled between December 2016 and November 2017. The median follow-up was 32.1 months. All patients received cisplatin concurrently with external beam radiotherapy combing with high-dose rate brachytherapy. Tumor tissues and PBMCs were collected before, during and after CCRT. We analyzed the changes in lymphocyte subpopulations, programmed death-1 (PD-1) and programmed cell death-1 ligand 1 (PD-L1) expression and the T-cell receptor (TCR) repertoire that occurred throughout CCRT.
RESULTS
The frequencies of CD4+ cells and PD-1+ T cells in PBMCs decreased after the start of CCRT, whereas that of inhibitory regulatory T cells increased. In the tumor tissues, CCRT decreased the numbers of CD4+ and CD8+ T cells and reduced the median percentage of positive cells expressing PD-L1 from 78.1% to 49.8%. As indicated by the numbers of unique clones, the TCR of PBMCs exhibited greater diversity before CCRT than after CCRT. Greater TCR diversity in PBMCs prior to CCRT was associated with superior 30-month progression-free survival (HR, 0.12 [95% CI, 0.04-0.39] p=0.001) and overall survival (HR, 0.17 [95% CI, 0.04-0.68], p=0.004).…
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