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

29 Citations (Scopus)

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

Fingerprint

Neoplasms
T-Lymphocytes
Immunologic Monitoring
Granzymes
Experimental Melanomas
Th1 Cells
Interleukin-18
p38 Mitogen-Activated Protein Kinases
Interleukin-12
Vaccination
Messenger RNA
Growth
Genes

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., ... 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

Gadd45b and Gadd45g are important for anti-tumor immune responses. / Ju, Songguang; Zhu, Yibei; Liu, Lin; Dai, Shao; Li, Changyou; Chen, Elizabeth; He, Yukai; Zhang, Xueguang; Lu, Binfeng.

In: European Journal of Immunology, Vol. 39, No. 11, 01.11.2009, p. 3010-3018.

Research output: Contribution to journalArticle

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, vol. 39, no. 11, pp. 3010-3018. https://doi.org/10.1002/eji.200839154
Ju, Songguang ; Zhu, Yibei ; Liu, Lin ; Dai, Shao ; Li, Changyou ; Chen, Elizabeth ; He, Yukai ; Zhang, Xueguang ; Lu, Binfeng. / Gadd45b and Gadd45g are important for anti-tumor immune responses. In: European Journal of Immunology. 2009 ; Vol. 39, No. 11. pp. 3010-3018.
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