1. Academic Validation
  2. CXCL13 as a Novel Immune Checkpoint for Regulatory B Cells and Its Role in Tumor Metastasis

CXCL13 as a Novel Immune Checkpoint for Regulatory B Cells and Its Role in Tumor Metastasis

  • J Immunol. 2022 May 15;208(10):2425-2435. doi: 10.4049/jimmunol.2100341.
Jun Ren 1 2 Tianxia Lan 2 Ting Liu 1 Yu Liu 2 Bin Shao 2 Ke Men 2 Yu Ma 1 Xiao Liang 1 Yu-Quan Wei 2 Min Luo 3 Xia-Wei Wei 3
Affiliations

Affiliations

  • 1 Department of Medical Genetics/Prenatal Diagnosis, West China Second Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China; and.
  • 2 Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Chengdu, Sichuan, People's Republic of China.
  • 3 Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Chengdu, Sichuan, People's Republic of China minluo_scu@163.com xiaweiwei@scu.edu.cn.
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.

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