Journal Article

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

2019

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adjuvant chemotherapy / Adult / Aged / Antigens / Apoptosis / Apoptosis - physiology / B7-H1 Antigen - blood / Biochemistry / Biology and Life Sciences / Cancer / Cancer therapies / Cancer treatment / Care and treatment / Cell death / Chemoradiotherapy / Chemoradiotherapy - methods / Chemotherapy / Clinical significance / Clinical trials / Colorectal cancer / Correlation / Disease-Free Survival / Enzyme-Linked Immunosorbent Assay / Enzymes / Female / Genetic aspects / Hospitals / Humans / Immune system / Immunohistochemistry / Kidney Neoplasms - blood / Kidney Neoplasms - drug therapy / Kidney Neoplasms - therapy / Leukemia / Ligands / Lung cancer / Lymphocytes / Lymphoma / Male / Medical prognosis / Medical research / Medicine and Health Sciences / Middle Aged / Mortality / Multivariate analysis / Neoadjuvant Therapy - methods / Patients / PD-1 protein / PD-L1 protein / Physical Sciences / Physiological aspects / Prognosis / Prospective Studies / Radiation therapy / Radiotherapy / Rectum / Research and Analysis Methods / Surgery / Therapeutic applications / Tumors