CXCL13 in Cancer and Other Diseases: Biological Functions, Clinical Significance, and Therapeutic Opportunities

Abstract

The development of cancer is a multistep and complex process involving interactions between tumor cells and the tumor microenvironment (TME). C-X-C chemokine ligand 13 (CXCL13) and its receptor, CXCR5, make crucial contributions to this process by triggering intracellular signaling cascades in malignant cells and modulating the sophisticated TME in an autocrine or paracrine fashion. The CXCL13/CXCR5 axis has a dominant role in B cell recruitment and tertiary lymphoid structure formation, which activate immune responses against some tumors. In most cancer types, the CXCL13/CXCR5 axis mediates pro-neoplastic immune reactions by recruiting suppressive immune cells into tumor tissues. Tobacco smoke and haze (smohaze) and the carcinogen benzo(a)pyrene induce the secretion of CXCL13 by lung epithelial cells, which contributes to environmental lung carcinogenesis. Interestingly, the knockout of CXCL13 inhibits benzo(a)pyrene-induced lung cancer and azoxymethane/dextran sodium sulfate-induced colorectal cancer in mice. Thus, a better understanding of the context-dependent functions of the CXCL13/CXCR5 axis in tumor tissue and the TME is required to design an efficient immune-based therapy. In this review, we summarize the molecular events and TME alterations caused by CXCL13/CXCR5 and briefly discuss the potentials of agents targeting this axis in different malignant tumors.

Bioinformatics Analysis of Prognostic Significance and Immune Characteristics of CXC Chemokine Family in Patients with Lung Adenocarcinoma

“…However, the findings of Fan et al were consistent with this present study [21]. Highly expressed CXCL13 and CXCL14 in lung cancer tissues were also reported in other studies [22,23].…”

CXCL13 chemokine is a novel player in multiple myeloma osteolytic microenvironment, M2 macrophage polarization, and tumor progression

“…CXCL13 was postulated to impact the proliferation, dissemination, and microenvironment interactions of several tumors, including solid cancers as well as hematological malignancies. Different cell types in the tumor milieu may overexpress CXCL13, including cancer cells, stromal and immune cells [ 34 ]. Dysregulated CXCL13 expression is seen in solid tumors including colorectal [ 35 ], breast [ 36 ], prostate [ 37 ], lung [ 38 ], and hepatocellular cancer [ 39 ] as well as lymphatic hematological malignancies like lymphoma [ 40 ] and CLL [ 20 ].…”

The Diagnostic Significance of CXCL13 in M2 Tumor Immune Microenvironment of Human Astrocytoma

“…As with recent studies, CXCL13/CD163 double staining results confirmed that CXCL13 is secreted by a variety of cells within the TME, including tumor cells and tumor-infiltrating immune cells. It specifically binds to the corresponding receptor CXCR5, directly regulating tumor progression or indirectly modulating adaptive immune responses ( 50 , 60 , 61 ). Notably, CXCL13 drives M2c activation through IL-10 induction and results in poor immunogenicity and immunosuppression ( 48 , 62 , 63 ).…”