Clinical significance of programmed death 1 ligand-1 (CD274/PD-L1) and intra-tumoral CD8+ T-cell infiltration in stage II-III colorectal cancer

Sci Rep. 2018 Oct 23;8(1):15658. doi: 10.1038/s41598-018-33927-5.

Abstract

Programmed cell death-1 (PDCD1/PD-1) and its ligand programmed cell death 1 ligand 1 (CD274/PD-L1) have been reported to suppress anti-tumor T cell-mediated immune responses. However, the clinical significance of CD274 in colorectal cancer were still elusive. We aim to clarify the relationships between CD8+ intratumor-infiltrating lymphocytes (TILs) and CD274 as well as their prognostic values in stage II-III colon carcinoma. Tumor differentiation, perineural invasion (PNI), pN stage and DNA mismatch repair (MMR)-deficient were clearly correlated with CD8+ TILs counts within the tumor microenvironment (p < 0.0001). Furthermore, tumor differentiation and PNI were suggestively correlated with tumor CD274 expression (p = 0.02 and p = 0.0195). Tumor CD274 level was significantly correlated with higher CD8+ TILs (p < 0.0001) but was not associated with MMR-deficient status (p = 0.14). High tumor CD274 expression [hazard ratio (HR) = 2.16, 95% CI = 1.63-2.86, p < 0.0001] and CD8+ TILs [HR = 1.51, 95% CI = 1.19-1.91, p = 0.0007] were associated with improved disease-free survival and overall survival. Additionally, the subgroup of patients who had a high CD8+ TILs/tumor CD274 have better survival outcomes compared with other subgroups (71% vs 53%; p < 0.0001). Therefore, the CD8+ TILs counts and tumor CD274 may be prognostic factors to predict survival and therapeutic responses in stage II-III colon carcinoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B7-H1 Antigen / analysis
  • B7-H1 Antigen / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology*
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Survival Analysis
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen
  • CD274 protein, human