Cancer Immunology, Immunotherapy

, Volume 57, Issue 1, pp 1–17

Anti-cancer therapies targeting the tumor stroma

  • Valeska Hofmeister
  • David Schrama
  • Jürgen C. Becker
Review

DOI: 10.1007/s00262-007-0365-5

Cite this article as:
Hofmeister, V., Schrama, D. & Becker, J.C. Cancer Immunol Immunother (2008) 57: 1. doi:10.1007/s00262-007-0365-5

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.

Keywords

AngiogenesisEndothelial cellsExtra-cellular matrixFibroblastsInvasionTherapy

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)

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Valeska Hofmeister
    • 1
  • David Schrama
    • 1
  • Jürgen C. Becker
    • 1
  1. 1.Department of DermatologyJulius-Maximilians-University of WuerzburgWuerzburgGermany