Table 1.
Therapeutic targets associated with the CXCL13/CXCR5 axis in malignancies and the tumor microenvironment.
| Target | Cancer Type | Function | Approach | In Vivo or In Vitro | Outcome | Refs. |
|---|---|---|---|---|---|---|
| CXCL13 | Prostate cancer | Induction of prostate cancer cell proliferation and migration | siRNA and shRNA; antibody | In vivo; in vitro | Inhibiting tumor growth and metastasis | [122] |
| CXCL13 | Prostate cancer | Chemotaxis B cells into regressing tumor | Antibody | In vivo | Preventing B-cell recruitment into tumor under castration | [115] |
| CXCL13 | Breast cancer | Activating CXCR5/ERK pathway | Polyclonal antibody | In vivo; in vitro | Attenuating tumor volume and growth; inhibiting tumor cell proliferation and promoting its apoptosis | [102,104] |
| CXCL13 | Breast cancer | Enhancing the production of RANKL on tumor cells and the interaction between ILC3 and stromal cells | Antibody | In vivo | Attenuating lymph node metastasis | [131] |
| CXCL13 | Lung cancer | Promotion of cell proliferation; inducing the production of SPP1 by microphage | Cxcl13−/− mice | In vivo | Decreasing the volume of BaP-induced tumor | [18] |
| CXCL13 | PDAC | Homing B cell into tumor lesions | Antibody | Mice harbored KrasG12D PDEC | Reducing the growth of orthotopic tumor | [116] |
| CXCL13 | Colon cancer | Induction 5-Fu resistance and association with a worse outcome | siRNA | In vitro | Reducing 5-Fu resistance | [112] |
| CXCR5 | CLL | CXCR5+ leukemia B cells recruited by CXCL13 to encounter proliferation stimuli | Cxcr5−/− Eμ-Tcl1 mice | In vivo | Attenuating tumor cell proliferation | [86] |
| CXCR5 | Prostate cancer | Induction of prostate cancer cells proliferation and migration | siRNA and shRNA | In vivo; in vitro | Inhibiting tumor growth and metastasis | [122] |
| CXCR5 | Lung cancer | CXCR5+ CD68+ macrophages producing SPP1 to promote EMT process | Cxcr5−/− mice | In vivo | Decreasing the volume of BaP-induced tumor | [18] |
| CXCR5 | OSCC | Induction RANKL expression under CXCL13/CXCR5 axis | Antibody | In vitro | Inhibiting the expression of RANKL | [74] |
| TGFβR | Prostate cancer | Activating CXCL13-expressing myofibroblasts | SB-431542 | In vivo | Blocking the initiation of castration-resistant prostate cancer | [87] |
| NFATc3 | OSCC | Nuclear translocation mediated by CXCL13/CXCR5 axis to bind to RANKL promoter region | siRNA | In vitro | Preventing RANKL expression | [74] |
| Myofibroblasts | Prostate cancer | Induction of CXCL13 expression | Immunodepletion; phosphodiesterase 5 | In vivo | Blocking the initiation of castration-resistant prostate cancer | [87] |
ILC3, RORγt+ innate lymphoid cell group 3; SPP1, secreted phosphoprotein 1; BaP, benzo(a)pyrene; PDAC, pancreatic ductal adenocarcinoma; PDEC, pancreatic ductal epithelial cells; 5-Fu, 5-Fluorouracil; CLL, chronic lymphocytic leukemia; EMT, epithelial to mesenchymal transition; OSCC, oral squamous cell carcinomas; RANKL, RANK ligand; TGFβR, TGFβ receptor; NFATc3, nuclear factor of activated T cells.