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Tumor stroma-associated antigens for anti-cancer immunotherapy

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Abstract

Immunotherapy has been widely investigated for its potential use in cancer therapy and it becomes more and more apparent that the selection of target antigens is essential for its efficacy. Indeed, limited clinical efficacy is partly due to immune evasion mechanisms of neoplastic cells, e.g. downregulation of expression or presentation of the respective antigens. Consequently, antigens contributing to tumor cell survival seem to be more suitable therapeutic targets. However, even such antigens may be subject to immune evasion due to impaired processing and cell surface expression. Since development and progression of tumors is not only dependent on cancer cells themselves but also on the active contribution of the stromal cells, e.g. by secreting growth supporting factors, enzymes degrading the extracellular matrix or angiogenic factors, the tumor stroma may also serve as a target for immune intervention. To this end several antigens have been identified which are induced or upregulated on the tumor stroma. Tumor stroma-associated antigens are characterized by an otherwise restricted expression pattern, particularly with respect to differentiated tissues, and they have been successfully targeted by passive and active immunotherapy in preclinical models. Moreover, some of these strategies have already been translated into clinical trials.

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Notes

  1. E. Gilboa, J. Lee, M. Fassnacht, S.K. Nair. Poster presented at the Keystone symposium “Cancer immunotherapy targeting the tumor stroma” in february 2005 in Fairmont Banff Springs, Canada with the title “The role of microenvironment in tumor induction and progression”, Abstract 138

Abbreviations

ADCC:

Antibody-dependent cellular cytotoxicity

CAF:

Cancer-associated fibroblast

CTL:

Cytotoxic T cell

ECM:

Extracellular matrix

IDO:

Indoleamine 2,3-dioxygenase

MHC:

Major histocompatibility complex

PSMA:

Prostate specific membrane antigen

TAA:

Tumor-associated antigen

TAM:

Tumor-associated macrophage

TEC:

Tumor endothelial cell

TEM:

Tumor endothelial marker

TIL:

Tumor-infiltrating lymphocyte

TSAA:

Tumor stroma-associated antigen

uPA:

Urokinase plasminogen activator

VEGF:

Vascular endohelial growth factor

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Acknowledgements

This work was supported by the DFG (Klinische Forschergruppe 124).

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  1. Department of Dermatology, Julius-Maximilians-University of Wuerzburg, Josef-Schneider-Str. 2, 97080, Wuerzburg, Germany

    Valeska Hofmeister, Claudia Vetter, David Schrama, Eva-B. Bröcker & Jürgen C. Becker

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  1. Valeska Hofmeister
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  2. Claudia Vetter
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Correspondence to Jürgen C. Becker.

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Hofmeister, V., Vetter, C., Schrama, D. et al. Tumor stroma-associated antigens for anti-cancer immunotherapy. Cancer Immunol Immunother 55, 481–494 (2006). https://doi.org/10.1007/s00262-005-0070-1

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