Abstract
BackgroundGlobally, colorectal carcinoma (CRC) is the third most common cancer diagnosed in both men and women. Programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are immune checkpoints that induce tumour immune escape.AimThis study aimed to evaluate the immunohistochemical expression of PD-L1 and CTLA-4 in CRC and their relationship with clinicopathological parameters and survival data.ResultThis study included 103 CRC, 22 adenoma and 21 non-neoplastic specimens. High PD-L1 epithelial expression was in favour of CRC and high-grade dysplastic adenoma compared to normal specimens. High PD-L1 epithelial expression was associated with larger sized tumours, perforation, advanced T stage, infiltrative tumour border configuration (TBC), high tumour budding (TB) score, low tumour-stroma ratio (TSR) and absence of peritumoural lymphocytes. High PD-L1+ tumour infiltrating lymphocytes (TILs) showed an association with absence of perforation, early T stage, pushing TBC, lower TB score, high TSR and presence of peritumoural lymphocytes. High epithelial CTLA-4 expression was in favour of adenocarcinoma, high-grade dysplastic adenoma and low-grade dysplastic adenoma compared to normal specimens. High CTLA-4 epithelial score showed an association with positive lymph nodes (LNs), presence of an infiltrative TBC and absence of peritumoural lymphocytes. Low CTLA-4+ TILs showed a significant association with advanced tumour stage and increased number of positive LNs. Prolonged survival was associated with low epithelial PD-L1 and CTLA-4, high PD-L1+ TILs and high CTLA-4+ TILs. By multivariate Cox regression analysis, PD-L1+ TILs immunoreactivity score (p = 0.020) and CTLA-4+ TILs H. score (p = 0.036) were independent prognostic factors affecting overall survival among the other prognostic factors.ConclusionPD-L1 and CTLA-4 expression by tumour cells could cooperate with each other in enhancing progression of CRC leading to poor patient outcome, while their expression by TILs could stand against tumour progression.
Highlights
Colorectal carcinoma (CRC) ranks third and second as regards incidence and mortality, respectively, among the most prevalent cancers, worldwide
Programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) expression by tumour cells could cooperate with each other in enhancing progression of CRC leading to poor patient outcome, while their expression by tumour infiltrating lymphocytes (TILs) could stand against tumour progression
This can be explained by presence of inherent tumoural signalling pathways, like PTEN gene deletion, which often leads to the over-activation of the phosphatidylinositol 3 kinase (PI3K)/Protein kinase B (AKT) signalling pathway, increasing PD-L1 expression, which will inhibit activation of cytotoxic T cells [32]
Summary
Colorectal carcinoma (CRC) ranks third and second as regards incidence and mortality, respectively, among the most prevalent cancers, worldwide. In 2020, more than 1.9 million new cases and 935,000 deaths occurred [1]. There is an increasing incidence of CRC among Egyptian patients, especially those who are ≤ 40 years of age [3]. Increased understanding of the immune tumour microenvironment (TME) allowed investigation of novel immune-based biomarkers and the development of new agents for blockade of immune checkpoint molecules to activate antitumour immunity [5]. Colorectal carcinoma (CRC) is the third most common cancer diagnosed in both men and women. Programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are immune checkpoints that induce tumour immune escape
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