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- Title
The role and relationship between programmed death ligand 1 and cytotoxic T lymphocyte-associated antigen-4 immunohisto-chemical expression in colorectal carcinoma patients: an impact on outcome.
- Authors
El Dein Mohameda, Asmaa Shams; El-Rebey, Hala Said; Abdelsamed AboElnasr, Lamia Sabry; Abdou, Asmaa Gaber
- Abstract
Background: Globally, 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. Aim: This study aimed to evaluate the immunohistochemical expression of PD-L1 and CTLA-4 in CRC and their relationship with clinicopathological parameters and survival data. Result: This 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. Conclusion: PD-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.
- Subjects
COLORECTAL cancer; IMMUNE checkpoint proteins; TUMOR-infiltrating immune cells; CYTOTOXIC T lymphocyte-associated molecule-4; PROGNOSIS; SPINAL tuberculosis
- Publication
Ecancermedicalscience, 2021, Vol 15, Issue 1316-1337, p1
- ISSN
1754-6605
- Publication type
Article
- DOI
10.3332/ecancer.2021.1323