Clinical significance of soluble programmed cell death-1 and soluble programmed cell death-ligand 1 in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

Tetsuro Tominaga,Noriko Yamamoto,Senzo Taguchi,Toshiya Nagasaki,Takashi Akiyoshi,Seiichi Mori,Yosuke Fukunaga,Masashi Ueno,Aamir Ahmad

doi:10.1371/journal.pone.0212978

Abstract

BackgroundInhibition of the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) axis in combination with radiotherapy may be a promising approach to treat cancer. In the present study, we aimed to evaluate serum soluble PD-1/PD-L1 levels in patients with advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT).MethodsSerum soluble PD-L1 and PD-1 levels were measured using an enzyme-linked immunosorbent assay before and after CRT in 117 patients with low rectal cancer. Changes in the levels of sPD-L1/PD-1 after CRT, and the correlation between sPD-L1/PD-1 level and clinicopathological characteristics or disease-free survival (DFS) were evaluated.ResultssPD-L1 levels significantly increased after CRT (p < 0.0001), whereas sPD-1 levels did not change significantly (p = 0.1050). High sPD-L1 before CRT was significantly associated with younger age (p = 0.044), and after CRT, with lymphovascular invasion (p = 0.021). High sPD-1 before and after CRT was significantly associated with a longer distance of the tumor from the anal verge (both p < 0.001). There was no correlation between sPD-L1 level and local PD-L1 expression on stromal immune cells. High sPD-L1 level after CRT tended to be associated with worse DFS (p = 0.0752). The multivariate analysis could not demonstrate an independent association for sPD-L1 levels after CRT with DFS.ConclusionsSignificant increase of sPD-L1 levels after CRT suggests that anti-PD-L1 therapy might be a potential treatment strategy in combination with CRT in advanced rectal cancer.

Highlights

Neoadjuvant chemoradiotherapy (CRT) is the standard of care for locally advanced rectal cancer
Results Soluble PD-L1 (sPD-L1) levels significantly increased after CRT (p < 0.0001), whereas soluble PD-1 (sPD-1) levels did not change significantly (p = 0.1050)
High sPD-L1 level after CRT tended to be associated with worse disease-free survival (DFS) (p = 0.0752)

Summary

Introduction

Neoadjuvant chemoradiotherapy (CRT) is the standard of care for locally advanced rectal cancer. Several randomized, controlled trials (RCTs) have demonstrated that neoadjuvant CRT reduces the local recurrence rate in these patients [1,2,3,4]. Novel treatment strategies are necessary to improve the oncological outcomes in patients with advanced rectal cancer. Programmed cell death-ligand 1 (PD-L1) is one of the ligands of PD-1[7] expressed on the surface of activated T cells and macrophage lineage cells or aberrantly expressed on tumors. Antibodies against PD-1 and PD-L1 can improve the clinical outcomes of patients with several different tumor types [8]. We aimed to evaluate serum soluble PD-1/PD-L1 levels in patients with advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT)

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