1. CXCL13 as a Novel Immune Checkpoint for Regulatory B Cells and Its Role in Tumor Metastasis
- Author
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Jun Ren, Tianxia Lan, Ting Liu, Yu Liu, Bin Shao, Ke Men, Yu Ma, Xiao Liang, Yu-quan Wei, Min Luo, and Xia-wei Wei
- Subjects
Mice, Inbred C57BL ,Tumor Immunology ,B-Lymphocytes, Regulatory ,Mice ,Neoplasms ,Immunology ,Tumor Microenvironment ,Animals ,Humans ,Immunology and Allergy ,Neoplasm Metastasis ,Chemokine CXCL13 ,Interleukin-10 - Abstract
Tumor metastasis is the primary cause of mortality in patients with cancer. Several chemokines are identified as important mediators of tumor growth and/or metastasis. The level of CXCL13 has been reported to be elevated in serum or tumor tissues in patients, which mainly functions to attract B cells and follicular B helper T cells. However, the role of CXCL13 in cancer growth and metastasis is not fully explored. In the current study, we found that CXCL13 is not a strong mediator to directly promote tumor growth; however, the mice deficient in CXCL13 had far fewer pulmonary metastatic foci than did the wild-type mice in experimental pulmonary metastatic models. In addition, Cxcl13−/− mice also had fewer IL-10–producing B cells (CD45+CD19+IL-10+) in the metastatic tumor immune microenvironment than those of wild-type C57BL/6 mice, resulting in an enhanced antitumor immunity. Notably, CXCL13 deficiency further improved the efficacy of a traditional chemotherapeutic drug (cyclophosphamide), as well as that of anti–programmed death receptor-1 immunotherapy. These results suggested that CXCL13 has an important role in regulating IL-10–producing B cells in tumor metastasis and might be a promising target for improving therapeutic efficiency and stimulating tumor immunity in future cancer therapy.
- Published
- 2022