Journal
JOURNAL OF CONTROLLED RELEASE
Volume 343, Issue -, Pages 303-313Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2022.01.039
Keywords
C -X -C motif chemokine ligand 13; Regulatory B cells; Desmoplastic tumor; Tumor-associated fibroblasts; Tumor microenvironment; Pancreatic cancer
Funding
- NIH [CA198999, CA157738]
- Packard Fellowship (SKL)
- Eshelman Institute for Innovation
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Interaction between different cell types in the tumor microenvironment affects tumor growth. Tumor-associated fibroblasts produce CXCL13, which recruits B cells to the tumor microenvironment. B cells in the tumor microenvironment differentiate into regulatory B cells (Bregs). CXCL13 also stimulates epithelial-mesenchymal transition (EMT) of tumor cells. Using plasmid DNA encoding a CXCL13 trap to reduce Bregs differentiation and normalize EMT suppresses tumor growth.
Interactions between different cell types in the tumor microenvironment (TME) affect tumor growth. Tumorassociated fibroblasts produce C-X-C motif chemokine ligand 13 (CXCL13) which recruits B cells to the TME. B-cells in the TME differentiate into regulatory B cells (Bregs) (IL-10+CD1d+CD5+CD138+CD19+). We highlight these Breg cells as a new important factor in the modulation of the immunosuppressive TME in different desmoplastic murine tumor models. In addition, CXCL13 also stimulates epithelial-mesenchymal transition (EMT) of the tumor cells. The tumorigenic roles of CXCL13 led us to explore an innovative anti-cancer strategy based on delivering plasmid DNA encoding a CXCL13 trap to reduce Bregs differentiation and normalize EMT, thereby suppressing tumor growth. CXCL13 trap suppressed tumor growth in pancreatic cancer, BRAF-mutant melanoma, and triple-negative breast cancer. In this study, following treatment, the affected tumor remained dormant resulting in prolonged progression-free survival of the host.
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