Three-dimensional scaffolds to evaluate tumor associated fibroblast-mediated suppression of breast tumor specific T cells

Vy Phan-Lai, Stephen J. Florczyk, Forrest M Kievit, Kui Wang, Ekram Gad, Mary L. Disis, Miqin Zhang

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1330-1337
Number of pages8
JournalBiomacromolecules
Volume14
Issue number5
DOIs
StatePublished - May 13 2013

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T-cells
Fibroblasts
Scaffolds
Tumors
Breast Neoplasms
T-Lymphocytes
Chitosan
Cells
Antigens
Neoplasms
Alginate
Tumor Microenvironment
Helper-Inducer T-Lymphocytes
Transforming Growth Factor beta
Interleukin-10
Immunotherapy
Immunosuppression
Immunity
Breast
Cancer-Associated Fibroblasts

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Three-dimensional scaffolds to evaluate tumor associated fibroblast-mediated suppression of breast tumor specific T cells. / Phan-Lai, Vy; Florczyk, Stephen J.; Kievit, Forrest M; Wang, Kui; Gad, Ekram; Disis, Mary L.; Zhang, Miqin.

In: Biomacromolecules, Vol. 14, No. 5, 13.05.2013, p. 1330-1337.

Research output: Contribution to journalArticle

Phan-Lai, Vy ; Florczyk, Stephen J. ; Kievit, Forrest M ; Wang, Kui ; Gad, Ekram ; Disis, Mary L. ; Zhang, Miqin. / Three-dimensional scaffolds to evaluate tumor associated fibroblast-mediated suppression of breast tumor specific T cells. In: Biomacromolecules. 2013 ; Vol. 14, No. 5. pp. 1330-1337.
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