Table 2.
Cancer treatment approaches targeting CCL19, -21/CCR7 and CXCL13/CXCR5 axes based on pre-clinical models.
| Target | Approach | Type of cancer | Works for the axis (in the TME) | In vitro or in vivo | Outcome | Ref. |
|---|---|---|---|---|---|---|
| CCL19, -21/CCR7 axis | ||||||
| CCL19 | Intratumoral CCL19 transduced with retroviral vector | Breast | (through a mechanism involving NK and CD4+ cells) | In vitro and in vivo | Reduction of tumor growth | [90] |
| CCL21 | Intratumoral recombinant CCL21 | Lung (alveolar carcinoma, LLC) | Induction of CD4+ cells, CTLs, and DCs, also in the draining lymph nodes | In vivo | Reduction of tumor growth | [91] |
| Intratumoral Ad-CCL21-DC | Lung (LLC) | Induction of CD4+ cells, CTLs, and DCs, reduction of Tregs, and upregulation of CXCL9 and CXCL10 | In vivo | Reduction of tumor growth (Depletion of CXCL9 and CXCL10 reduced the antitumor efficacy of Ad-CCL21-DC) | [92] | |
| Intratumoral Ad-CCL21-DC | Myeloma | Induction of CTLs | In vivo | Reduction of tumor growth | [93] | |
| Intratumoral CCL21 nanocapsule | Lung (LLC) | Induction of T cells and DCs, and reduction of MDSCs and Tregs | In vivo | Reduction of tumor growth | [94] | |
| Intratumoral Ad-CCL21-DC | Lung (NSCLC) | Induction of CTLs and tumor PD-L1 expression (and systemic tumor antigen–specific immune responses) | Phase I study | Twenty-five percent (4/16) of patients had stable disease at day 56. | [95] | |
| Anti-CCL21 antibodies | Melanoma | − | In vivo | Reduction of lymph node metastasis | [97] | |
| Inhibition of TGF(3Ip | CRC | Reduction of CCL21 expression in LECs and LEC permeability by inducing the dissociation of VE-cadherin junctions | In vivo | Reduction of tumor lymphangiogenesis and metastasis | [98] | |
| CCR7 | Anti-CCR7 antibody | Breast | Reduction of CCR7 expression in cancer cells | In vivo | Reduction of lymph node metastasis | [96] |
| TAK1 inhibitor, 5Z-O | Breast | Reduction of CCR7 expression in cancer cells | In vivo | Reduction of tumor lymphatic invasion and distant metastasis | [99] | |
| CXCL13/CXCR5 axis | ||||||
| CXCL13 | Intratumoral recombinant CXCL13 | CRC | - | In vivo | Reduction of tumor growth | [1] |
| CXCL13-coupled CpG oligonucleotides (CpG-ODN) | Breast cancer | Stimulation of B cells, inhibition of Bregs expressing low levels of CD20, and induction of CTLs | In vivo | Reduction of lung metastasis | [100] | |
| Anti-CXCL13 inhibitor | PDAC | Inhibitiing the migration of Bregs | In vivo | Reduction of tumor growth | [47] | |
| CXCR5 | CXCL13-KDEL intrakine (suppression of CXCR5) | CRC | Inhibition of CXCR5 function in cancer cells | In vitro and in vivo | Induction of tumor growth arrest in liver metastasis | [101] |
| (depletion of CXCR5) | Prostate | Inhibition of CXCR5 function mediated by NF-kB pathway in cancer cells | In vitro and in vivo | Reduction of tumor growth and metastasis | [17] | |
Note: CXCL13-KDEL intrakine, transfection of CXCL13 extended with a KDEL sequence
Abbreviations: Ad-CCL21-DC, autologous DCs transduced with an adenoviral (Ad) vector expressing the CCL21 gene; Bregs, regulatory B cells; CRC, colorectal cancer; CTLs, cytotoxic T lymphocytes; DCs, dendritic cells; LECS, lymphatic endothelial cells; LLC, Lewis lung cancer; MDSC, myeloid-derived suppressor sells; NSCLC, non-small-cell lung cancer; PDAC, pancreatic ductal adenocarcinoma; TAK1, TGF-β-activated protein kinase 1; TGFβIp, transforming growth factor-β (TGF-β)-induced protein; TME, tumor microenvironment; Tregs, regulatory T cells; 5Z-O, 5Z-7-oxozeaenol.