Lingeng Lu1, Yalai Bai2, Zuoheng Wang3. 1. Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale Cancer Center, Yale University, 60 College Street, New Haven, CT, 06520-8034, USA. lingeng.lu@yale.edu. 2. Department of Pathology, Yale University School of Medicine, New Haven, CT, 06520, USA. 3. Department of Biostatistics, Yale School of Public Health, School of Medicine, Yale Cancer Center, Yale University, 60 College Street, New Haven, CT, 06520-8034, USA.
Abstract
PURPOSE: Immune checkpoints cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death 1 receptor (PD-1) negatively regulate CD8+ T cell functions, impeding the capacity of effector T cells to kill tumors. Here, we study the prognostic significance of CTLA4, PD-1 and T cell activation status in breast cancer. METHODS: Using a publicly accessed RNA-seq dataset including 1087 breast cancer patients, we performed Kaplan-Meier survival curves and multivariate Cox regression models to evaluate the associations of CTLA4, PD-1, and weighted T cell activation score with patients' overall survival. RESULTS: Survival analyses showed that high CTLA4 but low PD-1 expression was associated with a poor overall survival, and that high T cell activation score was associated with an improved survival. The median survival was 216.6 months (95% CI 114.1-244.9) for the T activation group, 127.0 months (95% CI 112.3-212.1) for the intermediate, and 120.5 months (95% CI 93.8 to ∞) for the exhaustion (Log-rank p = 0.084). This association was verified in multivariate Cox regression analysis. The hazard ratios were 0.81 (95% CI 0.56-1.19) for the intermediate group, and 0.48 (95% CI 0.26-0.86) for the activation group, respectively, in comparison to the exhaustion group (p value for trend = 0.016). CONCLUSIONS: T cell activation score has significantly positive relationship with patients' overall survival, and may serve as a marker of personalized immunotherapy in breast cancer patients. Cocktail rather than single immune checkpoint blockade may yield more benefit for breast cancer patients.
PURPOSE: Immune checkpoints cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death 1 receptor (PD-1) negatively regulate CD8+ T cell functions, impeding the capacity of effector T cells to kill tumors. Here, we study the prognostic significance of CTLA4, PD-1 and T cell activation status in breast cancer. METHODS: Using a publicly accessed RNA-seq dataset including 1087 breast cancerpatients, we performed Kaplan-Meier survival curves and multivariate Cox regression models to evaluate the associations of CTLA4, PD-1, and weighted T cell activation score with patients' overall survival. RESULTS: Survival analyses showed that high CTLA4 but low PD-1 expression was associated with a poor overall survival, and that high T cell activation score was associated with an improved survival. The median survival was 216.6 months (95% CI 114.1-244.9) for the T activation group, 127.0 months (95% CI 112.3-212.1) for the intermediate, and 120.5 months (95% CI 93.8 to ∞) for the exhaustion (Log-rank p = 0.084). This association was verified in multivariate Cox regression analysis. The hazard ratios were 0.81 (95% CI 0.56-1.19) for the intermediate group, and 0.48 (95% CI 0.26-0.86) for the activation group, respectively, in comparison to the exhaustion group (p value for trend = 0.016). CONCLUSIONS: T cell activation score has significantly positive relationship with patients' overall survival, and may serve as a marker of personalized immunotherapy in breast cancerpatients. Cocktail rather than single immune checkpoint blockade may yield more benefit for breast cancerpatients.
Entities:
Keywords:
Breast cancer; CTLA4; PD-1; Prognosis; T cell activation score