Abstract

With respect to CD8 effector T cells, interleukin-12 (IL-12) and transforming growth factor β (TGFβ) are 2 cytokines that exert opposing effects. IL-12 promotes antitumor immune responses by augmenting activated CD8 T-cell proliferation and interferon-γ secretion. Conversely, TGFβ generates a permissive environment for cancer growth, in part by antagonizing the effects of immunomodulatory cytokines, including IL-12. We demonstrate that TGFβ-resistant T cells are capable of sustaining IL-12-induced mitogenesis and interferon-γ secretion in a TGFβ-rich milieu. Furthermore, in 2 murine tumor models associated with high TGFβ1 levels in the local microenvironment, treatment with IL-12 and adoptively transferred TGFβ-resistant T cells provided improved survival times. These results suggest that combining IL-12 with TGFβ neutralization strategies may be effective in enhancing antitumor immune responses.

Original languageEnglish (US)
Pages (from-to)479-489
Number of pages11
JournalJournal of Immunotherapy
Volume30
Issue number5
DOIs
StatePublished - Jul 1 2007

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Transforming Growth Factors
Interleukin-12
Immunity
T-Lymphocytes
Interferons
Cytokines
Neoplasms
Cell Proliferation
Growth

Keywords

  • Adoptive transfer
  • Brain cancer
  • Combination immunotherapy
  • Metastatic melanoma
  • Transgenic lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Enhancing antitumor immunity : Combining IL-12 with TGFβ1 antagonism. / Fan, Timothy M; Kranz, David M; Roy, Edward J.

In: Journal of Immunotherapy, Vol. 30, No. 5, 01.07.2007, p. 479-489.

Research output: Contribution to journalArticle

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N2 - With respect to CD8 effector T cells, interleukin-12 (IL-12) and transforming growth factor β (TGFβ) are 2 cytokines that exert opposing effects. IL-12 promotes antitumor immune responses by augmenting activated CD8 T-cell proliferation and interferon-γ secretion. Conversely, TGFβ generates a permissive environment for cancer growth, in part by antagonizing the effects of immunomodulatory cytokines, including IL-12. We demonstrate that TGFβ-resistant T cells are capable of sustaining IL-12-induced mitogenesis and interferon-γ secretion in a TGFβ-rich milieu. Furthermore, in 2 murine tumor models associated with high TGFβ1 levels in the local microenvironment, treatment with IL-12 and adoptively transferred TGFβ-resistant T cells provided improved survival times. These results suggest that combining IL-12 with TGFβ neutralization strategies may be effective in enhancing antitumor immune responses.

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