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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

Tominaga, T.; Akiyoshi, T.; Yamamoto, N.; Taguchi, S.; Mori, S.; Nagasaki, T.; Fukunaga, Y.; Ueno, M.

Plos one 14(2): E0212978

2019


ISSN/ISBN: 1932-6203
PMID: 30807610
DOI: 10.1371/journal.pone.0212978
Accession: 066533732

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Inhibition 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). Serum 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. sPD-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. Significant 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.

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