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Anti-cancer therapies targeting the tumor stroma

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

For anti-tumor therapy different strategies have been employed, e.g., radiotherapy, chemotherapy, or immunotherapy. Notably, these approaches do not only address the tumor cells themselves, but also the tumor stroma cells, e.g., endothelial cells, fibroblasts, and macrophages. This is of advantage, since these cells actively contribute to the proliferative and invasive behavior of the tumor cells via secretion of growth factors, angiogenic factors, cytokines, and proteolytic enzymes. In addition, tumor stroma cells take part in immune evasion mechanisms of cancer. Thus, approaches targeting the tumor stroma attract increasing attention as anti-cancer therapy. Several molecules including growth factors (e.g., VEGF, CTGF), growth factor receptors (CD105, VEGFRs), adhesion molecules (αvβ3 integrin), and enzymes (CAIX, FAPα, MMPs, PSMA, uPA) are induced or upregulated in the tumor microenvironment which are otherwise characterized by a restricted expression pattern in differentiated tissues. Consequently, these molecules can be targeted by inhibitors as well as by active and passive immunotherapy to treat cancer. Here we discuss the results of these approaches tested in preclinical models and clinical trials.

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Notes

  1. http://library.corporate-ir.net/library/63/639/63952/items/176589/6_MEDX120905_Nichol1.pdf.

Abbreviations

CAIX:

Carbonic anhydrase IX

CAF:

Cancer-associated fibroblast

CTGF:

Connective tissue growth factor

DPPIV:

Dipeptidyl peptidase IV

ECM:

Extra-cellular matrix

FAPα:

Fibroblast activation protein α

MHC:

Major histocompatibility complex

MMP:

Matrix metalloproteinase

(N)SCL(C):

(Non) small cell lung (cancer)

PAGRIT:

Pretargeted antibody guided radioimmunotherapy

PSMA:

Prostate-specific membrane antigen

SIP:

Small immunoprotein format

TAM:

Tumor-associated macrophage

TEC:

Tumor endothelial cell

TEM:

Tumor endothelial marker

TIMP:

Tissue inhibitor of metalloproteinases

uPA(R):

Urokinase plasminogen activator (receptor)

VEGF(R):

Vascular endohelial growth factor (receptor)

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Acknowledgments

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, David Schrama & Jürgen C. Becker

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  1. Valeska Hofmeister
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  2. David Schrama
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Correspondence to Jürgen C. Becker.

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Hofmeister, V., Schrama, D. & Becker, J.C. Anti-cancer therapies targeting the tumor stroma. Cancer Immunol Immunother 57, 1–17 (2008). https://doi.org/10.1007/s00262-007-0365-5

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