Gadd45b and Gadd45g are important for anti‐tumor immune responses |
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| Authors: | Songguang Ju Yibei Zhu Lin Liu Shao Dai Changyou Li Elizabeth Chen Yukai He Xueguang Zhang Binfeng Lu |
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| Affiliation: | 1. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;2. Institute of Medical Biotechnology, Soochow University, Suzhou, P. R. China;3. Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;4. University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA |
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| 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. |
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| Keywords: | CD8+ T cells Cytokines Interferons Signal transduction Tumor immunology |
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