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Nat Med. 2009 May;15(5):528-36. doi: 10.1038/nm.1953. Epub 2009 Apr 26.

Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies.

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1
The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.

Erratum in

  • Nat Med. 2009 Jul;15(7):819.

Abstract

Identifying key factors that enhance immune responses is crucial for manipulating immunity to tumors. We show that after a vaccine-induced immune response, adjuvant interleukin-7 (IL-7) improves antitumor responses and survival in an animal model. The improved immune response is associated with increased IL-6 production and augmented T helper type 17 cell differentiation. Furthermore, IL-7 modulates the expression of two ubiquitin ligases: Casitas B-lineage lymphoma b (Cbl-b), a negative regulator of T cell activation, is repressed, and SMAD-specific E3 ubiquitin protein ligase-2 (Smurf2) is enhanced, which antagonizes transforming growth factor-beta signaling. Notably, we show that although short term IL-7 therapy potently enhances vaccine-mediated immunity, in the absence of vaccination it is inefficient in promoting antitumor immune responses, despite inducing homeostatic proliferation of T cells. The ability of adjuvant IL-7 to antagonize inhibitory networks at the cellular and molecular level has major implications for immunotherapy in the treatment of tumors.

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PMID:
19396174
DOI:
10.1038/nm.1953
[Indexed for MEDLINE]
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