J Cancer 2019; 10(24):6175-6184. doi:10.7150/jca.35901

Research Paper

Clinical Implications of Tumor-Infiltrating Immune Cells in Breast Cancer

Shi-Chao Zhang1,2*, Zu-Quan Hu1,2*, Jin-Hua Long4, Gui-Ming Zhu2, Yun Wang1,2, Yi Jia1,2, Jing Zhou1,2, Yan Ouyang1,2✉, Zhu Zeng1,3✉

1. Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang 550025, China
2. Engineering Research Center of Medical Biotechnology, School of Biology and Engineering, Guizhou Medical University, Guiyang 550025, China
3. School of Basic Medical Science, Guizhou Medical University, Guiyang 550025, China
4. Affiliated Tumor Hospital, Guizhou Medical University, Guiyang 550004, China
*These authors contributed equally to this work.

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Citation:
Zhang SC, Hu ZQ, Long JH, Zhu GM, Wang Y, Jia Y, Zhou J, Ouyang Y, Zeng Z. Clinical Implications of Tumor-Infiltrating Immune Cells in Breast Cancer. J Cancer 2019; 10(24):6175-6184. doi:10.7150/jca.35901. Available from http://www.jcancer.org/v10p6175.htm

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Abstract

The immune infiltration of tumors is closely related to clinical outcomes. The composition of tumor-infiltrating immune cells (TIICs) can serve as biomarkers for predicting response to treatment and survival in different patient subgroups in terms of chemotherapy and immunotherapy. This study is focused on investigating the clinical implications of TIICs in breast cancer patients. We performed several in silico analyses of gene expression profiles in 2976 nonmetastatic tumor samples. CIBERSORT was used to estimate the proportion of 22 immune cell types to analyze their correlation with overall survival (OS) and disease-free survival (DFS) in different breast cancer subtypes and stages. Our results showed that a higher fraction of plasma cells in estrogen receptor (ER)-positive breast cancer patients indicated an increase in DFS (hazard ratio [HR]=0.66, 95% confidence interval [CI] 0.54~0.82, p<0.01), while a decreased OS was correlated with a greater number of M0 macrophages (HR=2.02, 95% CI 1.27~3.30, p=0.01) and regulatory T cells (HR=1.90, 95% CI 1.20~3.02, p=0.02). In ER-negative or progesterone receptor (PR)-negative subtypes or in a combined subtype, the increase in activated memory CD4+ T cells was correlated with increased DFS (HR=0.46, 95% CI 0.33~0.63, p<0.01). In all breast cancer patients, a higher proportion of M0 macrophages indicated a decreased DFS (HR=1.67, 95% CI 1.22~2.27, p<0.01), while increased OS was associated with relatively larger fractions of resting memory CD4+ T cells (HR=0.70, 95% CI 0.55~0.90, p=0.02) and γδ T cells (HR=0.66, 95% CI 0.51~0.85, p<0.01). Therefore, this study revealed that the composition of TIICs is different in patients with various subtypes of breast cancer and is directly related to prognosis, suggesting that TIICs are important participants in tumor progression and may, potentially be used for future diagnosis and treatment.

Keywords: breast cancer, tumor-infiltrating immune cells (TIICs), prognosis, disease-free survival (DFS), overall survival (OS)