Concurrent Chemoradiotherapy Increases the Levels of Soluble Immune Checkpoint Proteins in Patients with Locally Advanced Cervical Cancer

Abstract

Concurrent chemoradiotherapy (CCRT) could influence systematic immunity in cancer patients, but its impact on soluble immune checkpoint molecules remain largely unknown. Here, we investigated the dynamic alterations of 16 soluble immune checkpoint molecules in locally advanced cervical cancer (LACC) patients treated with CCRT. Sixty LACC patients treated with CCRT were prospectively enrolled and patients’ blood was collected before, during, and at the end of CCRT. Sixteen soluble immune checkpoint molecules were tested by Luminex platform. Tumor response was evaluated based on RECIST 1.1 guidelines at one month after CCRT. One-way analysis of variance with Bonferroni's post-test or paired t tests were used to evaluate the change of the levels of soluble immune checkpoint molecules. Forty-five (75%) patients experienced complete response (CR), 12 (20%) patients experienced partial response (PR), and 3 (5%) patients experienced stable disease after CCRT. Levels of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) increased both during and at the end of CCRT (P = .015 and .003, respectively), while inducible T-cell costimulator (ICOS), B7-2, glucocorticoid-induced tumor necrosis factor receptor ligand (GITRL) increased at the end of CCRT (P = .032, .048, and .050, respectively). The other soluble immune checkpoint molecules including CD40 showed no significant change throughout CCRT (all P >0.05). Interestingly, we found that these changes were more significant in patients with CR than patients with PR/SD. Specifically, for patients with CR, levels of TIM-3 were significantly elevated both during and at the end of CCRT (P = .008 and < .001, respectively), while ICOS, B7-2, GITRL were significantly elevated at the end of CCRT (P = .023, .039, and .042, respectively). Meanwhile, CD40 was significantly elevated at the end of CCRT in patients with CR (P = .040). However, patients with PR/SD, no soluble immune checkpoint molecules were significantly changed (all P > 0.05). Our study reveals that CCRT could induce the elevation of the levels of soluble TIM-3, ICOS, B7-2, and GITRL in the blood of patients with LACC. This phenomenon was more obvious in patients with good response to CCRT.