Abstract
Purpose/background
Radiotherapy has been recently reported to boost the therapeutic response of immune checkpoint blockade (ICB); however, few studies have focused on programmed cell death-ligand 1 (PD-L1) expression in locally advanced rectal cancer (LARC) patients who receive preoperative neoadjuvant chemoradiotherapy (neoCRT). The aim of the present study was to investigate the PD-L1 expression status and CD8+ intra-tumoral infiltrating lymphocytes (TILs) before and after neoCRT and its association with clinicopathological characteristics in rectal cancer.
Materials and methods
Immunostainings of PD-L1 and CD8+ TILs were performed in 112 pair-matched LARC patients treated by neoCRT. Tumor PD-L1 expression and CD8+ TILs within the tumor microenvironment before and after neoCRT were evaluated via immunohistochemistry.
Results
High tumor PD-L1 expression was significantly increased from 50 to 63%, and high CD8+ TILs counts were also slightly increased from 32 to 35% after neoCRT treatment. High tumor PD-L1 before and after neoCRT was associated with improved disease-free survival (DFS, pre-neoCRT: p = 0.003 and post-neoCRT: p = 0.003) and overall survival (OS, pre-neoCRT: p = 0.045 and post-neoCRT: p = 0.0001). High CD8+ TILs before neoCRT was associated with improved DFS (p = 0.057), and it was significantly associated with improved DFS after neoCRT (p = 0.039). Patients with high tumor PD-L1 and CD8+ TILs before and after neoCRT were significantly associated with improved DFS (pre-neoCRT: p = 0.004 and post-neoCRT: p = 0.006).
Conclusion
The present results provide evidence that tumor PD-L1 expression and recruitment of CD8+ TILs within the tumor microenvironment were increased by neoCRT treatment. Tumor PD-L1 and CD8+ TILs are prognostic biomarkers for the survival of LARC patients treated with neoCRT.
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Acknowledgements
We are grateful for the tissue microarray support from the Translation Research Core, China Medical University Hospital. This study is supported in part by China Medical University Hospital (DMR-107-061), Ministry of Science and Technology Ministry of Science and Technology (MOST107-2314-B-039-027-MY3 and MOST107-2314-B-039-057-MY3, Taiwan), and Ministry of Health and Welfare (MOHW107-TDU-B-212-123004, Taiwan), Health and welfare surcharge of tobacco products, China Medical University Hospital Cancer Research Center of Excellence (MOHW108-TDU-B-212-124024, Taiwan).
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T-WC, S-FC and KC-YH conducted and performed the experiments; WT-LC, T-WK and T-WC enrolled the LARC patients and performed IHC evaluation; S-FC and KSCC supervised this study; S-FC, and KSCC analyzed the data and wrote the manuscript.
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This study was reviewed and approved by the Internal Review Board (IRB) of China Medical University Hospital [Protocol number: CMUH105-REC2-072].
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Chen, TW., Huang, K.CY., Chiang, SF. et al. Prognostic relevance of programmed cell death-ligand 1 expression and CD8+ TILs in rectal cancer patients before and after neoadjuvant chemoradiotherapy. J Cancer Res Clin Oncol 145, 1043–1053 (2019). https://doi.org/10.1007/s00432-019-02874-7
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DOI: https://doi.org/10.1007/s00432-019-02874-7