Three-Dimensional Scaffolds to Evaluate Tumor Associated Fibroblast-Mediated Suppression of Breast Tumor Specific T Cells
Year: 2013
Type: article
Abstract: In the tumor microenvironment, the signals from tumor-associated fibroblasts (TAF) that suppress antitumor immunity remain unclear. Here, we develop and investigate an in vitro three-dimensional (3D) scaffold model for the novel evaluation of TAF interaction with breast tumor cells and breast specific, neu antigen (p98) reactive T cells. Breast cancer cells seeded on 3D chitosan-alginate (CA) scaffolds showed productive growth and formed distinct tumor spheroids. Antigen specific p98 T cells, but not naïve T cells, bound significantly better to tumor cells on scaffolds. The p98 T cells induced potent tumor cell killing but T helper cell cytokine function was impaired in the presence of TAF coseeding on scaffolds. We found that the immunosuppression was mediated, in part, by transforming growth factor beta (TGF-b) and interleukin-10 (IL-10). Therefore, TAF appear capable of inducing potent T cell suppression. CA scaffolds can provide clinically relevant findings prior to preclinical testing of novel immunotherapies.
Source: Biomacromolecules
DOI: 10.1021/bm301928u
Authors: Vy Phan-Lai, Stephen J. Florczyk, Forrest M. Kievit, Kui Wang, Ekram Gad, Mary L. Disis, Miqin Zhang
Institution: University of Washington
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: Multifuctional Nanovector For Diagnosis And Treatment Of Pediatric Brain Cancer, Institute for Translational Health Science (UL1), Nanovectors For Brain Tumor Diagnosis And Treatment, Nanotechnology and Physical Science Training Program in Cancer Research, Optimized ex vivo expansion of anti-tumor Th1 and Tc1 for adoptive immunotherapy
OpenAlex ID: W2057781728