Abstract
Purpose
To investigate the associations between programmed cell death ligand-1 (PD-L1) on tumor cells (TCs) or PD-L1 on tumor-infiltrating immune cells (TIICs) and the microsatellite instability (MSI) status in colorectal cancer (CRC).
Methods
In total, 238 CRC patients were enrolled. PD-L1 expression and MSI status were studied by immunohistochemical staining and polymerase chain reaction. The χ2 test was used to compare characteristics. The Kaplan–Meier method was used for survival analysis. Cox proportional hazards models were used to determine the prognostic influence of clinicopathological factors.
Results
Eighteen patients (7.6%) were had MSI-high (MSI-H) CRC. The number of patients with PD-L1 expression on TCs, stromal TIICs and intraepithelial TIICs was 13 (5.5%), 64 (26.9%) and 45 (18.9%), respectively. The MSI-H phenotype was significantly associated with younger age, right sidedness, mucinous component, high grade, stromal TIICs expressing PD-L1 (P = 0.042) and intraepithelial TIICs expressing PD-L1 (P < 0.001), but not TCs expressing PD-L1. PD-L1-expressing TCs were an independent marker of poor prognosis [hazard ratio (HR) = 3.387, P = 0.003], and PD-L1-expressing stromal TIICs were an independent marker of good prognosis (HR = 0.551, P < 0.001).
Conclusions
PD-L1-expressing TCs were a marker of poor prognosis; in contrast, PD-L1-expressing TIICs were a marker of good prognosis. The MSI-H phenotype was associated with the presence of PD-L1-expressing TIICs, but not of PD-L1-expressing TCs.
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Acknowledgements
We are thankful for grants from the Taiwan Clinical Oncology Research Foundation, Ministry of Health and Welfare, Taiwan (MOHW107-TDU-B-211-114019), Taipei Veterans General Hospital (107DHA0100381 and 108DHA0100103) and Yen Tjing Ling Medical Foundation (CI-108-19). The authors would like to acknowledge the support from the Biobank of Taipei Veterans General Hospital and Precision Medicine Envision Project, Taipei Veterans General Hospital.
Funding
This study was funded by grants from the Taiwan Clinical Oncology Research Foundation, Ministry of Health and Welfare, Taiwan (MOHW107-TDU-B-211-114019), Taipei Veterans General Hospital (107DHA0100381 and 108DHA0100103) and Yen Tjing Ling Medical Foundation (CI-108-19).
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The authors Hsiang-Ling Ho, Teh-Ying Chou, Shung-Haur Yang, Jeng-Kai Jiang, Wei-Shone Chen, Yee Chao, and Hao-Wei Teng declare that they have no conflict of interest.
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This retrospective study was conducted using data from Taipei Veterans General Hospital, Taipei, Taiwan and under the guidelines of the Declarations of Helsinki; it was approved by the Human Subjects Protection Offices at Taipei Veterans General Hospital. The medical residual samples of the patients with CRC were acquired from the residual sample bank of Taipei Veterans General Hospital. VGHIRB waived the requirement for the use of an informed consent form.
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Informed consent was not obtained prior to analysis in this study (VGHIRB waived the requirement for the use of an inform consent form).
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Ho, HL., Chou, TY., Yang, SH. et al. PD-L1 is a double-edged sword in colorectal cancer: the prognostic value of PD-L1 depends on the cell type expressing PD-L1. J Cancer Res Clin Oncol 145, 1785–1794 (2019). https://doi.org/10.1007/s00432-019-02942-y
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DOI: https://doi.org/10.1007/s00432-019-02942-y