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Ovarian cancer progression is controlled by phenotypic changes in dendritic cells.

Publication ,  Journal Article
Scarlett, UK; Rutkowski, MR; Rauwerdink, AM; Fields, J; Escovar-Fadul, X; Baird, J; Cubillos-Ruiz, JR; Jacobs, AC; Gonzalez, JL; Weaver, J ...
Published in: J Exp Med
March 12, 2012

We characterized the initiation and evolution of the immune response against a new inducible p53-dependent model of aggressive ovarian carcinoma that recapitulates the leukocyte infiltrates and cytokine milieu of advanced human tumors. Unlike other models that initiate tumors before the development of a mature immune system, we detect measurable anti-tumor immunity from very early stages, which is driven by infiltrating dendritic cells (DCs) and prevents steady tumor growth for prolonged periods. Coinciding with a phenotypic switch in expanding DC infiltrates, tumors aggressively progress to terminal disease in a comparatively short time. Notably, tumor cells remain immunogenic at advanced stages, but anti-tumor T cells become less responsive, whereas their enduring activity is abrogated by different microenvironmental immunosuppressive DCs. Correspondingly, depleting DCs early in the disease course accelerates tumor expansion, but DC depletion at advanced stages significantly delays aggressive malignant progression. Our results indicate that phenotypically divergent DCs drive both immunosurveillance and accelerated malignant growth. We provide experimental support for the cancer immunoediting hypothesis, but we also show that aggressive cancer progression after a comparatively long latency period is primarily driven by the mobilization of immunosuppressive microenvironmental leukocytes, rather than loss of tumor immunogenicity.

Duke Scholars

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Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

March 12, 2012

Volume

209

Issue

3

Start / End Page

495 / 506

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Transforming Growth Factor beta1
  • RNA, Messenger
  • Proto-Oncogene Proteins p21(ras)
  • Phenotype
  • Ovarian Neoplasms
  • Models, Immunological
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
 

Citation

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Scarlett, U. K., Rutkowski, M. R., Rauwerdink, A. M., Fields, J., Escovar-Fadul, X., Baird, J., … Conejo-Garcia, J. R. (2012). Ovarian cancer progression is controlled by phenotypic changes in dendritic cells. J Exp Med, 209(3), 495–506. https://doi.org/10.1084/jem.20111413
Scarlett, Uciane K., Melanie R. Rutkowski, Adam M. Rauwerdink, Jennifer Fields, Ximena Escovar-Fadul, Jason Baird, Juan R. Cubillos-Ruiz, et al. “Ovarian cancer progression is controlled by phenotypic changes in dendritic cells.J Exp Med 209, no. 3 (March 12, 2012): 495–506. https://doi.org/10.1084/jem.20111413.
Scarlett UK, Rutkowski MR, Rauwerdink AM, Fields J, Escovar-Fadul X, Baird J, et al. Ovarian cancer progression is controlled by phenotypic changes in dendritic cells. J Exp Med. 2012 Mar 12;209(3):495–506.
Scarlett, Uciane K., et al. “Ovarian cancer progression is controlled by phenotypic changes in dendritic cells.J Exp Med, vol. 209, no. 3, Mar. 2012, pp. 495–506. Pubmed, doi:10.1084/jem.20111413.
Scarlett UK, Rutkowski MR, Rauwerdink AM, Fields J, Escovar-Fadul X, Baird J, Cubillos-Ruiz JR, Jacobs AC, Gonzalez JL, Weaver J, Fiering S, Conejo-Garcia JR. Ovarian cancer progression is controlled by phenotypic changes in dendritic cells. J Exp Med. 2012 Mar 12;209(3):495–506.

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

March 12, 2012

Volume

209

Issue

3

Start / End Page

495 / 506

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Transforming Growth Factor beta1
  • RNA, Messenger
  • Proto-Oncogene Proteins p21(ras)
  • Phenotype
  • Ovarian Neoplasms
  • Models, Immunological
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice