期刊
BIOMACROMOLECULES
卷 14, 期 5, 页码 1330-1337出版社
AMER CHEMICAL SOC
DOI: 10.1021/bm301928u
关键词
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资金
- NIH [R01CA134213, R01EB006043]
- Kyocera Professorship Endowment [UL1RR025014, R01 CA136632]
- Ruth L. Kirschstein NIH Training Grant [T32 CA138312]
- Egtvedt Scholarship
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 TAP 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 g spheroids. Antigen specific p98 T cells, but not naive 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 TAP 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, TAP appear capable of inducing potent T cell suppression. CA scaffolds can provide clinically relevant findings prior to preclinical testing of novel immunotherapies.
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