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CXCL13 expression in mouse 4T1 breast cancer microenvironment elicits antitumor immune response by regulating immune cell infiltration.

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机构： [1]Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China. [2]Institute of Drug Clinical Trial, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China. [3]Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, and Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China.

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关键词： CXCL13 triplenegativebreastcancer 4T1 tumormicroenvironment CXCR5

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Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer-related deaths among women worldwide. Previous studies have reported contradictory performance of chemokine CXC motif ligand 13 (CXCL13) in breast cancer. In this study, The Cancer Genome Atlas database analysis revealed that CXCL13 was overexpressed in various human cancers including breast carcinoma, and associated with good clinical prognosis in breast cancer. Flow cytometry detection also found upregulated intracellular CXCL13 expression in human breast cancer cell lines. To explore the possible role of CXCL13 in the breast cancer microenvironment, mouse triple negative breast cancer (TNBC) was lentivirally transfected to stably overexpress mouse CXCL13 (4T1-CXCL13). Both parental 4T1 and 4T1-CXCL13 strains showed no in vitro or in vivo endogenous cell surface CXCR5 expression. In immune-competent BALB/c mice, the in vivo tumor growth of 4T1-CXCL13 was significantly inhibited and even completely eradicated, accompanied with increased infiltrations of CD4+, CD8+ T lymphocytes and CD11b+CD11c+ DCs. Further investigations showed that CXCL13 expression in the 4T1 tumor microenvironment elicited long-term antitumor immune memory, and rejection of distal parental tumor. The antitumor activity of CXCL13 was remarkedly impaired in BALB/cA-nu nude mice, or in BALB/c mice with CD8+ T lymphocyte or NK cell depletion. Our investigation indicated that CXCL13 expression in TNBC triggered effective antitumor immunity by chemoattracting immune cell infiltrations and could be considered as a novel prognostic marker for TNBC.© The Author(s) 2021. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.

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大类 | 4 区医学

小类 | 4 区医学：研究与实验

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大类 | 4 区医学

小类 | 4 区医学：研究与实验

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第一作者机构： [1]Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.

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