4.6 Article

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

Journal

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 145, Issue 4, Pages 1043-1053

Publisher

SPRINGER
DOI: 10.1007/s00432-019-02874-7

Keywords

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

Categories

Funding

  1. China Medical University Hospital [DMR-107-061]
  2. Ministry of Science and Technology (Taiwan) [MOST107-2314-B-039-027-MY3, MOST107-2314-B-039-057-MY3]
  3. Ministry of Health and Welfare (Taiwan) [MOHW107-TDU-B-212-123004]
  4. Health and welfare surcharge of tobacco products, China Medical University Hospital Cancer Research Center of Excellence (Taiwan) [MOHW108-TDU-B-212-124024]

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Purpose/backgroundRadiotherapy 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 methodsImmunostainings 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.ResultsHigh 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).ConclusionThe 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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