Log in

Le rôle des modèles murins en immuno-oncologie

Role of murine models in immuno-oncology

  • Actualités en Immunologie / News in Immunology
  • Published:
Oncologie

Résumé

Les modèles précliniques en cancérologie sont généralement utilisés pour tester des hypothèses générées grâce à la recherche fondamentale. Les expériences sur les modèles murins sont ainsi réalisées avant qu’un essai clinique ne soit entrepris chez l’homme. Bien que cette stratégie ait conduit à de nombreuses découvertes dans le domaine de l’immunothérapie, elle présente néanmoins plusieurs inconvénients. Pour cette raison, une approche bidirectionnelle itérative doit aujourd’hui être prise en considération. Dans un article récemment publié dans la revue Cancer Immunol Res, les défis de l’utilisation des modèles murins en immuno-oncologie ont été abordés. En même temps que les études précliniques participent au développement clinique, les données obtenues sur l’humain doivent également être utilisées pour générer de nouvelles hypothèses à tester sur les modèles animaux.

Abstract

Preclinical models in oncology are generally used to test hypotheses generated through basic science. Thus, experiments on murine models are carried out prior to conduct a clinical trial involving humans. Although this strategy has initially led to many discoveries in the field of immunotherapy, it has several disadvantages. Due to this reason, an iterative bidirectional approach should be considered. In a recent article published in Cancer Immunol Res, the challenges in the use of murine models in immunooncology were described in an interesting way. Indeed, at the same time than preclinical studies contribute to clinical development, human clinical data should also be used to generate new hypotheses to be tested in animal models.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Références

  1. Tivol EA, Borriello F, Schweitzer AN, et al (1995) Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3:541–7

    Article  CAS  PubMed  Google Scholar 

  2. Waterhouse P, Penninger JM, Timms E, et al (1995) Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270:985–8

    Article  CAS  PubMed  Google Scholar 

  3. Leach DR, Krummel MF, Allison JP (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science 271:1734–6

    Article  CAS  PubMed  Google Scholar 

  4. Curran MA, Montalvo W, Yagita H, Allison JP (2010) PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci USA 107:4275–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Begley CG, Ellis LM (2012) Drug development: raise standards for preclinical cancer research. Nature 483:531–3

    Article  CAS  PubMed  Google Scholar 

  6. Gould SE, Junttila MR, de Sauvage FJ (2015) Translational value of mouse models in oncology drug development. Nat Med 21:431–9

    Article  CAS  PubMed  Google Scholar 

  7. Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G (2008) Immunological aspects of cancer chemotherapy. Nat Rev Immunol 8:59–73

    Article  CAS  PubMed  Google Scholar 

  8. Flanagan SP (1966) “Nude”, a new hairless gene with pleiotropic effects in the mouse. Genet Res 8:295–309

    Article  CAS  PubMed  Google Scholar 

  9. Mellman I, Hubbard-Lucey VM, Tontonoz MJ, et al (2016) Derisking immunotherapy: report of a consensus workshop of the cancer immunotherapy consortium of the Cancer Research Institute. Cancer Immunol Res 4:279–88

    Article  CAS  PubMed  Google Scholar 

  10. Feig C, Jones JO, Kraman M, et al (2013) Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci USA 110:20212–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Garin-Chesa P, Old LJ, Rettig WJ (1990) Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Proc Natl Acad Sci USA 87:7235–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Schiraldi M, Raucci A, Muñoz LM, et al (2012) HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med 209:551–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Beatty GL, Chiorean EG, Fishman MP, et al (2011) CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 331:1612–6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Vonderheide RH, Flaherty KT, Khalil M, et al (2007) Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J Clin Oncol 25:876–83

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to D. Grazziotin-Soares or J.-P. Lotz.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grazziotin-Soares, D., Lotz, JP. Le rôle des modèles murins en immuno-oncologie. Oncologie 19, 399–403 (2017). https://doi.org/10.1007/s10269-017-2731-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10269-017-2731-z

Mots clés

Keywords

Navigation