Cancer and Metastasis Reviews

, Volume 30, Issue 1, pp 83–95

Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy

  • Eric Tartour
  • H. Pere
  • B. Maillere
  • M. Terme
  • N. Merillon
  • J. Taieb
  • F. Sandoval
  • F. Quintin-Colonna
  • K. Lacerda
  • A. Karadimou
  • C. Badoual
  • A. Tedgui
  • W. H. Fridman
  • S. Oudard
Article

Abstract

The immune system regulates angiogenesis in cancer with both pro- and antiangiogenic activities. The induction of angiogenesis is mediated by tumor-associated macrophages and myeloid-derived suppressor cells (MDSC) which produce proinflammatory cytokines, endothelial growth factors (VEGF, bFGF…), and protease (MMP9) implicated in neoangiogenesis. Some cytokines (IL-6, IL-17…) activated Stat3 which also led to the production of VEGF and bFGF. In contrast, other cytokines (IFN, IL-12, IL-21, and IL-27) display an antiangiogenic activity. Recently, it has been shown that some antiangiogenic molecules alleviates immunosuppression associated with cancer by decreasing immunosuppressive cells (MDSC, regulatory T cells), immunosuppressive cytokines (IL-10, TGFβ), and inhibitory molecules on T cells (PD-1). Some of these broad effects may result from the ability of some antiangiogenic molecules, especially cytokines to inhibit the Stat3 transcription factor. The association often observed between angiogenesis and immunosuppression may be related to hypoxia which induces both neoangiogenesis via activation of HIF-1 and VEGF and favors the intratumor recruitment and differentiation of regulatory T cells and MDSC. Preliminary studies suggest that modulation of immune markers (intratumoral MDSC and IL-8, peripheral regulatory T cells…) may predict clinical response to antiangiogenic therapy. In preclinical models, a synergy has been observed between antiangiogenic molecules and immunotherapy which may be explained by an improvement of immune status in tumor-bearing mice after antiangiogenic therapy. In preclinical models, antiangiogenic molecules promoted intratumor trafficking of effector cells, enhance endogenous anti-tumor response, and synergyzed with immunotherapy protocols to cure established murine tumors. All these results warrant the development of clinical trials combining antiangiogenic drugs and immunotherapy.

Keywords

Angiogenesis Immunity Antiangiogenic Immunosuppression Immunotherapy Biomarker 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Eric Tartour
    • 1
    • 2
    • 8
  • H. Pere
    • 1
  • B. Maillere
    • 3
  • M. Terme
    • 1
  • N. Merillon
    • 1
  • J. Taieb
    • 1
    • 4
  • F. Sandoval
    • 1
  • F. Quintin-Colonna
    • 1
    • 5
  • K. Lacerda
    • 1
  • A. Karadimou
    • 1
    • 6
  • C. Badoual
    • 1
    • 7
  • A. Tedgui
    • 1
  • W. H. Fridman
    • 2
  • S. Oudard
    • 1
    • 6
  1. 1.INSERM U970 PARCC (Paris Cardiovascular Research Center)Universite Paris DescartesParisFrance
  2. 2.Service d’Immunologie BiologiqueHôpital Européen Georges Pompidou. Paris. AP-HPParisFrance
  3. 3.Commissariat à l’Energie Atomique-Saclay, Institut de Biologie et TechnologiesService d’Ingénierie Moléculaire des ProtéinesGif-sur-YvetteFrance
  4. 4.Unité d’Oncologie Digestive, Service d’HépatogastroentérologieHôpital Européen Georges Pompidou. Paris. AP-HPParisFrance
  5. 5.Ecole Nationale Vétérinaire d’AlfortMaisons-AlfortFrance
  6. 6.Service d’Oncologie MédicaleHôpital Européen Georges Pompidou. Paris. AP-HPParisFrance
  7. 7.Service d’Anatomie PathologieHôpital Européen Georges Pompidou. Paris. AP-HPParisFrance
  8. 8.Hôpital Européen Georges PompidouUnité d’immunologie biologiqueParisFrance

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