Effect of extracellular matrix components and tumors factors from breast cancer on the biological properties of myeloid cells in the mouse model

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B972
Abstract ID: 7642

Presenting Author:
Fabian Benencia , Associate Professor of Immunology at Univ. of Ohio Heritage Col. of Osteopathic Med.

Abstract:

The tumor microenvironment (TME) is composed of cells and extracellular matrix (ECM) components that oftentimes help cancer cells to survive and growth. Immune cells, whose role is to protect against infections or malignancies, can be coopted by the TME or reprogrammed by tumor factors rendering them incapable of fighting the tumor inducing a protumor phenotype. Key immune cells affected in this process are antigen presenting cells (APCs) such as dendritic cells (DC) and macrophages (Macs). The effect of soluble factors produced by tumors (i.e., VEGF and TGF beta) on these cells has been broadly studied, but other factors such as extracellular matrix components can also alter their biology. Herewith, we were able to determine that APCs infiltrating the TME of the 4T1 model of breast cancer express angiogenic factors and chemokine receptors. In addition, we observed that tumor factors were able to induce migration of DCs and Macs. Furthermore, we detected markers of proliferation in tumor-infiltrating APCs, indicating that these cells might also be able to proliferate within the TME. We observed that tumor supernatants can activate these APCs invitro, and that this activation is partially mediated via TLR4 signaling. Finally, we observed that tumor cells and mouse tumors produce both fibronectin and fibronectin-extracellular domain (a known DAMP and activator of TLR4). Thus, production of ECM components by tumor cells can help shape the phenotype of tumor-associated APCs.