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. 2019 Apr;145(4):1043-1053. doi: 10.1007/s00432-019-02874-7. Epub 2019 Mar 14.

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / biosynthesis*
  • B7-H1 Antigen / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Chemoradiotherapy, Adjuvant
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Rectal Neoplasms / immunology*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / therapy*
  • Tumor Microenvironment / immunology

Substances

  • B7-H1 Antigen
  • CD274 protein, human