The role and relationship between programmed death ligand 1 and cytotoxic T lymphocyte-associated antigen-4 immunohistochemical expression in colorectal carcinoma patients; an impact on outcome

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.

Immunohistochemical Expression of Immune Checkpoints; CTLA-4, LAG3, and TIM-3 in Cancer Cells and Tumor-infiltrating Lymphocytes (TILs) in Colorectal Carcinoma

“…However, after surgery, more than 40% of those with CRC experience local relapse and distant metastases. 2 The primary factors affecting the individuals' prognosis with operable CRC are distant metastases and postoperative tumor recurrence. Local immune state, tumor malignancy, and distant metastasis (DM) are the main causes of cancer metastasis and relapse.…”

“…CTLA-4 and Tim-3 were expressed as brownish cytoplasmic/membranous staining and were assessed in TILs and cancer cells and scored as follows: 2,26 A scale from 0 to 3 was used to grade the degree of CRC cell staining (0 = negative, 1 = mild staining, 2 = moderate staining, and 3 = strong staining. To arrive at the final score, the epithelial intensity score was split into low (0, 1) and High (2, 3), while the stromal H score was split into low (mean) and high ( > mean).…”

“…CRC is becoming more common in Egyptian individuals, particularly those under 40. 2 Specific therapies utilizing immune checkpoint antibodies have had encouraging outcomes in treating various cancers, notably lung carcinoma, melanoma, urothelial carcinoma, and renal cell carcinoma. 3 Tumor-derived immune dysregulation is a fundamental characteristic of CRC.…”

“…As a result, they contribute to the development of a favorable microenvironment that promotes the ongoing growth of cancer cells. 2 Monoclonal anti-TIM-3, anti-CTLA-4, and anti-LAG3 antibodies efficiently inhibit these cascades, causing tumor-reactive cells to reawaken and clonally expand. Clinical trials on people with cancer, notably those with non-small cell lung cancer and melanoma, were remarkably successful.…”

PYCR1, BANF1, and STARD8 Expression in Gastric Carcinoma: A Clinicopathologic, Prognostic, and Immunohistochemical Study

“…12,13 Antigen retrieval was achieved with 10 mmol/l sodium citrate for 24 minutes. The primary antibody was incubated for 16 minutes using rabbit monoclonal antibodies versus primary antibodies against rabbit monoclonal (PYCR1, 1:2000; Proteintech, [14][15][16][17] ) anti-BANF1 antibody [18][19][20][21] (1:100) with mouse anti-STARD8 (1:1,000; [22][23][24][25] Abcam) overnight at 4°C. Tissues were fixed in formalin 10%, and an automated method was used.…”