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

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

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.

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Acknowledgements

We thank Dr. Liqiong Gui at Yale School of Medicine for her critical comments.

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Authors and Affiliations

  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

  2. 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

    Zuoheng Wang

  3. Department of Pathology, Yale University School of Medicine, New Haven, CT, 06520, USA

    Yalai Bai

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  1. Lingeng Lu
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Correspondence to Lingeng Lu.

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All procedures performed in this study involving human subjects followed the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. The study presented here complies with the current laws of the United States of America.

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Lu, L., Bai, Y. & Wang, Z. Elevated T cell activation score is associated with improved survival of breast cancer. Breast Cancer Res Treat 164, 689–696 (2017). https://doi.org/10.1007/s10549-017-4281-x

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