Chemoradiation-Induced Alteration of Programmed Death-Ligand 1 and CD8+ Tumor-Infiltrating Lymphocytes Identified Patients With Poor Prognosis in Rectal Cancer: A Matched Comparison Analysis

Yu Jin Lim, Jaemoon Koh, Sehui Kim, Sang Rok Jeon, Eui Kyu Chie, Kyubo Kim, Gyeong Hoon Kang, Sae Won Han, Tae You Kim, Seung Yong Jeong, Kyu Joo Park, Hong Gyun Wu

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43 Scopus citations

Abstract

Purpose To evaluate chemoradiotherapy (CRT)-induced changes in the expression levels of programmed death-ligand 1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) and prognostic associations in rectal cancer. Methods and Materials We performed a paired analysis using pre-CRT biopsies and the corresponding post-CRT resected tissues of 123 rectal cancer patients undergoing preoperative CRT followed by surgery between 2005 and 2012. Immunohistochemistry of PD-L1 and CD8 was analyzed for the specimens. Results The expression levels of PD-L1 and density of CD8+ TILs increased after CRT (P<.001 for both). With cutoffs using each median value, sustained higher expression of PD-L1 at pre- and post-CRT (high-to-high) was associated with less increase in the density of CD8+ TILs (P=.020). Patients representing sustained high-to-high PD-L1 expression had poorer overall survival and disease-free interval on univariate Kaplan-Meier analysis (P=.018 and.029, respectively), with inferior disease-free interval in low-to-low density CD8+ TILs (P=.010). On multivariate analysis, 2 subgroups with high baseline PD-L1 expression level, the high-to-low and high-to-high alterations, showed worse overall survival (hazard ratio 8.34, 95% confidence interval 1.85-37.53 and hazard ratio 11.03, 95% confidence interval 2.33-52.29, respectively), with the highest mortality risk observed in the high-to-high group. Conclusions This study verified the CRT-induced immunologic shift toward increases in PD-L1 expression and density of CD8+ TILs in rectal cancer patients. The alteration profiles of checkpoint-related molecules identified the patients with poor prognosis, suggesting potential candidates who can benefit from combining CRT and checkpoint inhibitors.

Original languageEnglish
Pages (from-to)1216-1224
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume99
Issue number5
DOIs
StatePublished - 1 Dec 2017

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