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

Autor:	Abdelrahman DI; Departments of Pathology., Elhasadi I; Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi, Libya., Anbaig A; Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi, Libya., Bakry A; Medical Oncology., Mandour D; Clinical Oncology., Wasefy T; General Surgery, Faculty of Medicine, Zagazig University, Zagazig., Yehia AM; General Surgery, Faculty of Medicine, Zagazig University, Zagazig., Alorini M; Department of Basic Medical Sciences, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah., Shalaby AM; Histology and Cell Biology, Faculty of Medicine, Tanta University, Tanta, Egypt., Yahia AIO; Department of Pathology, College of Medicine, University of Bisha, Bisha, Saudi Arabia.; Department of Pathology, Faculty of Medicine and Health Sciences, University of Kordofan, Elobeid, Sudan., Alabiad MA; Departments of Pathology.
Jazyk:	angličtina
Zdroj:	Applied immunohistochemistry & molecular morphology : AIMM [Appl Immunohistochem Mol Morphol] 2024 Feb 01; Vol. 32 (2), pp. 71-83. Date of Electronic Publication: 2023 Dec 18.
DOI:	10.1097/PAI.0000000000001181
Abstrakt:	Background: Colorectal cancer is considered the third most prevalent cancer in both sexes. Immune checkpoint receptors that regulate T-cell response, stimulation, and development include lymphocyte activating gene 3 (LAG-3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and T-cell immunoglobulin and mucin domain 3 (Tim-3). In addition, they are crucial for the advancement of cancer and tumor immune escape. Objective: This work's aim was to assess the immunohistochemistry expression of Tim-3, CTLA-4, and LAG-3 in cancer cells and tumor-infiltrating lymphocytes (TILs) in colorectal cancer (CRC) and the correlation between these markers and clinicopathological variables and survival data. Methods: This study involved 206 CRC specimens processed for CTLA-4, LAG3, and TIM-3 immunohistochemistry and correlated with the clinicopathological and survival parameters of the patients. Results: High CTLA-4 epithelial expression was highly related to the old age group, large tumor size, low tumor-stroma ratio (TSR), high grade, advanced stage, the presence of distant metastasis (DM), perineural invasion (PNI), necrosis, lymphovascular invasion (LVI), relapse, mortality, overall survival (OS), and disease-free survival (DFS), while negative CTLA-4 TILs expression was highly linked with the presence of gross perforation, low TSR, high tumor budding (TB) score, high grade, advanced stage, the existence of lymph node (LN) metastasis, DM, necrosis, LVI, PNI, DFS, mortality, and OS. Positive LAG-3 TILs expression was highly correlated with large tumor size, gross perforation, low TSR, high TB score, high grade, advanced phase, the presence of LN, necrosis, LVI, PNI, relapse DFS, mortality, and OS. High Tim-3 epithelial expression was extremely linked with low TSR, advanced phase, the presence of LN, LVI, PNI, relapse, DFS, mortality, and OS, while positive Tim-3 TILs expression was related to gross perforation, low TSR, high TB score, advanced stage, the presence of LN, DM, necrosis, relapse, DFS, mortality, and OS. Conclusions: The patients' poor prognosis may be related to the immunohistochemistry expression of LAG-3, Tim-3, and CTLA-4 in CRC cancer tissue and TILs. Poor patient consequences can result from the CTLA-4, Tim-3, and LAG-3 co-expression, but CTLA-4 TILs' expression of these proteins may inhibit the growth of tumors. Competing Interests: The authors declare no conflict of interest. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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