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Breast Cancer Res Treat. 2017 Aug;164(3):689-696. doi: 10.1007/s10549-017-4281-x. Epub 2017 May 9.

Elevated T cell activation score is associated with improved survival of breast cancer.

Author information

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.

KEYWORDS:

Breast cancer; CTLA4; PD-1; Prognosis; T cell activation score

PMID:
28488141
DOI:
10.1007/s10549-017-4281-x
[Indexed for MEDLINE]

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