방사선의학 웹진

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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.

Author information

Lim YJ1, Koh J2, Kim S2, Jeon SR3, Chie EK4, Kim K5, Kang GH2, Han SW6, Kim TY6, Jeong SY7, Park KJ7, Wu HG8.

1
Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea; Department of Radiation Oncology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Korea.
2
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
3
Cancer Research Institute, Seoul National University, Seoul, Korea.
4
Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University, Seoul, Korea.
5
Department of Radiation Oncology, Ewha Womans University School of Medicine, Seoul, Korea.
6
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
7
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
8
Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University, Seoul, Korea; Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea. Electronic address: wuhg@snu.ac.kr.