Abstract
Background and objectives: Cytotoxic T-lymphocyte (CTL)-mediated inflammatory response to tumors plays a crucial role in preventing the progression of some cancers. Programmed cell death ligand 1 (PD-L1), a cell-surface glycoprotein, has been reported to repress T-cell-mediated immune responses against tumors. However, the clinical significance of PD-L1 in colorectal cancer (CRC) remains unclear. Our aim was to elucidate the prognostic significance of PD-L1 expression and CD8+ CTL density in CRC. Materials and methods: CD8 and PD-L1 immunostaining was conducted on 157 pathologic specimens from patients with CRC. The CD8+ CTL density and PD-L1 expression within the tumor microenvironment were assessed by immunohistochemistry. Results: Tumor invasion (pT) was significantly correlated with intratumoral (p = 0.011) and peritumoral (p = 0.016) CD8+ CTLs density in the tumor microenvironment. In addition, there was a significant difference in the intensity of CD8+ CTLs between patients with and without distant metastases (intratumoral p = 0.007; peritumoral p = 0.037, T-test). Lymph node metastasis (pN) and TNM stage were significantly correlated with PD-L1 expression in CRC cells (p = 0.015, p = 0.029, respectively). Multivariate analysis revealed a statistically significant relationship between the intratumoral CD8+ CTL density and disease-free survival (DFS) (hazard ratio [HR] 2.06; 95% confidence interval [CI]: 1.01–4.23; p = 0.043). The DFS was considerably shorter in patients with a high expression of PD-L1 in cancer cells than those with a low expression (univariate HR 2.55; 95% CI 1.50–4.34; p = 0.001; multivariate HR 0.48; 95% CI 0.28–0.82; p = 0.007). Conversely, patients with high PD-L1 expression in tumor-infiltrating lymphocytes had a longer DFS in both univariate analysis (HR 0.25; 95% CI: 0.14–0.44; p < 0.001) and multivariate analysis (HR 3.42; 95% CI: 1.95–6.01; p < 0.001). Conclusion: The CD8+ CTL density and PD-L1 expression are prognostic biomarkers for the survival of patients with CRC.
Highlights
Colorectal cancer (CRC), one of the most common malignancies, is a major contributor to cancer-related deaths worldwide, and its incidence is increasing in developing countries
The disease-free survival (DFS) was considerably shorter in patients with a high expression of Programmed cell death ligand 1 (PD-L1) in cancer cells than those with a low expression
No differences were noted in sex, tumor size, or histologic grade in terms of DFS, whereas statistically significant correlations were noted for age, tumor site, histopathologic type, pT, pN, distant metastasis, and TNM stage versus DFS (Table 1)
Summary
Colorectal cancer (CRC), one of the most common malignancies, is a major contributor to cancer-related deaths worldwide, and its incidence is increasing in developing countries. It is estimated that in 2018 there will be more than 1.8 million new colorectal cancer cases and 881,000 deaths [1,2,3,4]. Physicians generally use a tumor-node-metastasis (TNM) staging system to estimate the prognosis of this cancer, but patients with the same stage or histologic grade. Cytotoxic T-lymphocyte (CTL)-mediated inflammatory response to tumors plays a crucial role in preventing the progression of some cancers. The clinical significance of PD-L1 in colorectal cancer (CRC). The CD8+ CTL density and PD-L1 expression within the tumor microenvironment were assessed by immunohistochemistry.
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