Gadd45b and Gadd45g are important for anti-tumor immune responses.
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-gamma, 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-gamma. 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.
Ju
Songguang
S
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Zhu
Yibei
Y
Liu
Lin
L
Dai
Shao
S
Li
Changyou
C
Chen
Elizabeth
E
He
Yukai
Y
Zhang
Xueguang
X
Lu
Binfeng
B
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D007157:Immunologic Surveillance / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D000097642:GADD45 Proteins
D000943:Antigens, Differentiation; D002352:Carrier Proteins; D007371:Interferon-gamma; D047908:Intracellular Signaling Peptides and Proteins; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins; C121373:Gadd45g protein, mouse
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