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

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Fingerprint Dive into the research topics of 'Enhancing antitumor immunity: Combining IL-12 with TGFβ1 antagonism'. Together they form a unique fingerprint.

  • Cite this