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Prognostic relevance of programmed cell death-ligand 1 expression and CD8+ TILs in rectal cancer patients before and after neoadjuvant chemoradiotherapy

  • Tsung-Wei Chen
  • Kevin Chih-Yang Huang
  • Shu-Fen Chiang
  • William Tzu-Liang Chen
  • Tao-Wei Ke
  • K. S. Clifford ChaoEmail author
Original Article – Clinical Oncology
  • 72 Downloads

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.

Keywords

Neoadjuvant chemoradiotherapy Programmed cell death 1 ligand 1 CD8 Tumor-infiltrating lymphocyte Locally advanced rectal cancer 

Notes

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).

Author contributions

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was reviewed and approved by the Internal Review Board (IRB) of China Medical University Hospital [Protocol number: CMUH105-REC2-072].

Informed consent

Informed consents were obtained from all participants in the study.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Graduate Institute of Biomedical ScienceChina Medical UniversityTaichungTaiwan
  2. 2.Department of PathologyChina Medical University Hospital, China Medical UniversityTaichungTaiwan
  3. 3.Translation Research CoreChina Medical University Hospital, China Medical UniversityTaichungTaiwan
  4. 4.Department of NutritionHungKuang UniversityTaichungTaiwan
  5. 5.Cancer CenterChina Medical University Hospital, China Medical UniversityTaichungTaiwan
  6. 6.Department of Colorectal SurgeryChina Medical University Hospital, China Medical UniversityTaichungTaiwan

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