ArticleFrontiers in immunology2025
CD155-TIGIT/CD96/CD226 immune checkpoint axis interacting with tumor-infiltrating lymphocytes to exhibit diverse prognostic effects on breast cancer: a cohort study.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Revisiting the Prognostic Significance of CD155 in Invasive Breast Carcinoma.Iranian journal of pathology · 2026Article
- The Right Key, the Wrong Lock: TIGIT Checkpoint Blockade and the Road to Precision Immunotherapy.Pharmaceutics · 2026Review
- Review
- LAG3 as a potential biomarker in breast cancer: integrated tissue and peripheral blood analysis reveals clinical and pathomic insights in triple-negative disease.Journal of translational medicine · 2026Article
- Diet, hormones, and breast cancer: biomarker-guided assessment of risk and prognosis.Frontiers in immunology · 2026Review
- Poliovirus receptor (PVR) expression as a predictor of relapse in colorectal cancer: bioinformatics and virtual screening.Experimental biology and medicine (Maywood, N.J.) · 2026Article
- The role of immune checkpoint molecules in cancers.Frontiers in immunology · 2025Review
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10 authors.
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Abstract
Background: CD155, an immune checkpoint molecule interacted with receptors of TIGIT/CD96/CD226 to exhibit co-inhibitory and co-stimulatory modulation on tumor immune microenvironment. Nevertheless, the exploration of collectively prognostic effect of these four molecules on breast cancer (BC) was limited. This study aimed to investigate the prognosis effect of CD155-TIGIT/CD96/CD226 complex in BC. Methods: CD155-TIGIT/CD96/CD226 expression was evaluated by immunohistochemistry in tumor microenvironment (TME) by pathological professionals and the associations with clinical characteristics and prognosis were investigated under a cohort study design. Results: CD155 was detected on TME tumor cells (TC) and TIGIT/CD96/CD226 were detected on both TC and stromal tumor-infiltrated lymphocytes (TILs). The four molecules showed significant correlation with clinicopathological characteristics and prognosis. High CD155 was associated with relapse (HR = 2.21, 95%CI:1.18-4.13) and death (HR = 2.57, 95%CI:1.29-5.10). High expression of CD226 (HR = 1.79, 95%CI:1.03-3.11) and CD96 (HR = 2.65, 95%CI:1.09-6.44) on TC was correlated with high risk of relapse. High expression of TIGIT on TILs was related to poor prognosis of relapse (HR = 2.06, 95%CI:1.02-4.14), while the expression on TC was a protective factor for relapse (HR = 0.45, 95%CI:0.24-0.83) and death (HR = 0.32, 95%CI:0.16-0.66). Additionally, tumoral and stromal expression of these biomarkers interacted with TME infiltration of stromal TILs to exhibit the diverse prognosis effect. Conclusion: The CD155-CD226/TIGIT/CD96 immune checkpoint complex expressed on both TME TC and TILs, and interacted with TILs to exhibit diverse prognosis effect on BC. The immunotherapy against these checkpoint proteins should check the expression on both TC and TILs and further studies should explore the molecule complex collectively for comprehensive prediction of BC prognosis.
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