Gadd45b and Gadd45g are important for anti-tumor immune responses

Songguang Ju, Yibei Zhu, Lin Liu, Shao Dai, Changyou Li, Elizabeth Chen, Yukai He, Xueguang Zhang, Binfeng Lu

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

An effective Th1 type cell-mediated immune response against cancer cells is critical in limiting cancer progression. Gadd45b, a signaling molecule highly up-regulated during Th1 type responses, is studied for its role in limiting tumor growth. Mouse B16 melanoma cells implanted into Gadd45b-/- mice grew faster than those in WT or Gadd45b+/- littermate controls. The defect of Gadd45b-/- mice in tumor immunosurveillance was attributed to the reduced expression of IFN-γ, granzyme B, and CCR5 in Gadd45b -/- CD8+ T cells at the tumor site. Activation of p38 MAP kinase, but not ERK or JNK, by either TCR-stimuli or IL-12 and IL-18 is diminished in Gadd45b-/- CD8+ T cells, resulting in reduced production of IFN-γ. In addition, mRNA of T-bet and Eomes were reduced in Gadd45b-/- CD8+ T cells, supporting a critical role of Gadd45b in shaping the Th1 fate. More importantly, the tumor vaccination, which is effective in WT mice, failed in Gadd45b/Gadd45g doubly deficient mice. Collectively, these data demonstrate that members of the Gadd45 gene family are important for anti-tumor immune responses.

Original languageEnglish (US)
Pages (from-to)3010-3018
Number of pages9
JournalEuropean Journal of Immunology
Volume39
Issue number11
DOIs
StatePublished - Nov 1 2009

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Keywords

  • CD8 T cells
  • Cytokines
  • Interferons
  • Signal transduction
  • Tumor immunology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Ju, S., Zhu, Y., Liu, L., Dai, S., Li, C., Chen, E., He, Y., Zhang, X., & Lu, B. (2009). Gadd45b and Gadd45g are important for anti-tumor immune responses. European Journal of Immunology, 39(11), 3010-3018. https://doi.org/10.1002/eji.200839154