Breadcrumb

Sigrid P. Dubois, Ph.D.

Sigrid P. Dubois, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute

RESEARCH SUMMARY

One of the Dr. Dubois' major contributions has been the characterization of the mechanism of action of IL-15. Instead of acting as a soluble factor, IL-15Ralpha retains IL-15 via a high-affinity interaction on the cell surface and trans-presents it to neighboring NK and CD8+ T cells that express IL-2/15Rbeta and gammac. Studies conducted by Dr. Dubois have helped in understanding the regulation of IL-15 production and its role in the development of some CD8 populations as well as its contribution to the activation/proliferation of NK cells. Dr. Dubois has been involved in the use of IL-15 in the treatment of malignancies in mice, where it has been found to be effective. Ultimately, the work of Dr. Dubois contributed to the GMP production of IL-15 that has been used in a first-in-human clinical trial as a new therapy for patients with metastatic malignant melanoma and renal cell cancer. Currently, two main projects conducted by Dr. Dubois focus on: 1) the role of IL-15 in the development of T cell malignancy, and 2) the development of a new therapy supporting the anti-tumor activity of NK cells.

Areas of Expertise

1) IL-15

Publications

Selected Publications

Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer

Zhang M, Yao Z, Dubois S, Ju W, Müller JR, Waldmann TA.
Proc. Natl. Acad. Sci. U.S.A.. 106: 7513-8, 2009. [ Journal Article ]

Preassociation of IL-15 with IL-15R alpha-IgG1-Fc enhances its activity on proliferation of NK and CD8+/CD44high T cells and its antitumor action

Dubois S, Patel HJ, Zhang M, Waldmann TA, Müller JR.
J. Immunol.. 180: 2099-106, 2008. [ Journal Article ]

IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells

Dubois S, Mariner J, Waldmann TA, Tagaya Y.
Immunity. 17: 537-47, 2002. [ Journal Article ]

Paracrine and transpresentation functions of IL-15 are mediated by diverse splice versions of IL-15Ra in human monocytes and dendritic cells

Müller JR, Waldmann TA, Kruhlak MJ, Dubois S.
J. Biol. Chem.. 287: 40328-38, 2012. [ Journal Article ]

Selective dependence of H2-M3-restricted CD8 responses on IL-15

Müller JR, Waldmann TA, Dubois S.
J. Immunol.. 188: 2575-82, 2012. [ Journal Article ]