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Cancer Microenvironment

, Volume 3, Issue 1, pp 29–47 | Cite as

T Cells and Stromal Fibroblasts in Human Tumor Microenvironments Represent Potential Therapeutic Targets

  • Jennifer L. Barnas
  • Michelle R. Simpson-Abelson
  • Sandra J. Yokota
  • Raymond J. KelleherJr.
  • Richard B. BankertEmail author
Review Paper

Abstract

The immune system of cancer patients recognizes tumor-associated antigens expressed on solid tumors and these antigens are able to induce tumor-specific humoral and cellular immune responses. Diverse immunotherapeutic strategies have been used in an attempt to enhance both antibody and T cell responses to tumors. While several tumor vaccination strategies significantly increase the number of tumor-specific lymphocytes in the blood of cancer patients, most vaccinated patients ultimately experience tumor progression. CD4+ and CD8+ T cells with an effector memory phenotype infiltrate human tumor microenvironments, but most are hyporesponsive to stimulation via the T cell receptor (TCR) and CD28 under conditions that activate memory T cells derived from the peripheral blood of the cancer patients or normal donors. Attempts to identify cells and molecules responsible for the TCR signaling arrest of tumor-infiltrating T cells have focused largely upon the immunosuppressive effects of tumor cells, tolerogenic dendritic cells and regulatory T cells. Here we review potential mechanisms by which human T cell function is arrested in the tumor microenvironment with a focus on the immunomodulatory effects of stromal fibroblasts. Determining in vivo which cells and molecules are responsible for the TCR arrest in human tumor-infiltrating T cells will be necessary to formulate and test strategies to prevent or reverse the signaling arrest of the human T cells in situ for a more effective design of tumor vaccines. These questions are now addressable using novel human xenograft models of tumor microenvironments.

Keywords

Cancer Fibroblast Immunotherapy Stromal cell T lymphocyte TCR signal transduction Tumor microenvironment Xenograft model 

Abbreviations

DC

dendritic cell

TAF

tumor-associated fibroblast

MDSC

myeloid-derived suppressor cell

MSC

mesenchymal stem cell

TIL

tumor-infiltrating T cells

TCR

T cell receptor

TGF-β1

Transforming growth factor-β1

Notes

Acknowledgement

This work was supported by National Institute of Health grants R01CA108970, R01CA131407, and R56AI079188.

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Jennifer L. Barnas
    • 1
  • Michelle R. Simpson-Abelson
    • 1
  • Sandra J. Yokota
    • 1
  • Raymond J. KelleherJr.
    • 1
  • Richard B. Bankert
    • 1
    Email author
  1. 1.Department of Microbiology and Immunology, Witebsky Center, School of Medicine and Biomedical SciencesUniversity at Buffalo, The State University of New YorkBuffaloUSA

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