TY - JOUR
T1 - Gadd45b and Gadd45g are important for anti-tumor immune responses
AU - Ju, Songguang
AU - Zhu, Yibei
AU - Liu, Lin
AU - Dai, Shao
AU - Li, Changyou
AU - Chen, Elizabeth
AU - He, Yukai
AU - Zhang, Xueguang
AU - Lu, Binfeng
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - CD8 T cells
KW - Cytokines
KW - Interferons
KW - Signal transduction
KW - Tumor immunology
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U2 - 10.1002/eji.200839154
DO - 10.1002/eji.200839154
M3 - Article
C2 - 19688743
AN - SCOPUS:70449363636
SN - 0014-2980
VL - 39
SP - 3010
EP - 3018
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 11
ER -