Abstract
STAT4 and STAT6 are essential for the development of CD4(+) Th1 and Th2 development, respectively. Tumor immunologists have hypothesized that Th1 cells are critical in tumor immunity because they facilitate differentiation of CD8(+) T cells, which are potent anti-tumor effectors. We have used STAT4(-/-) and STAT6(-/-) mice to test this hypothesis. BALB/c and knockout mice were challenged in the mammary gland with the highly malignant and spontaneously metastatic BALB/c-derived 4T1 mammary carcinoma. Primary tumor growth and metastatic disease are reduced in STAT6(-/-) mice relative to BALB/c and STAT4(-/-) mice. Ab depletions demonstrate that the effect is mediated by CD8(+) T cells, and immunized STAT6(-/-) mice have higher levels of 4T1-specific CTL than BALB/c or STAT4(-/-) mice. Surprisingly, Th1 or Th2 cells are not involved, because CD4 depletion does not diminish the anti-tumor effect. Therefore, deletion of the STAT6 gene facilitates development of potent anti-tumor immunity via a CD4(+)-independent pathway.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bone Marrow Neoplasms / genetics
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Bone Marrow Neoplasms / immunology
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Bone Marrow Neoplasms / prevention & control
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Bone Marrow Neoplasms / secondary
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Brain Neoplasms / genetics
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Brain Neoplasms / immunology
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Brain Neoplasms / prevention & control
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Brain Neoplasms / secondary
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Division / genetics
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Cell Division / immunology
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Cytotoxicity, Immunologic / genetics
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Disease Progression
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Liver Neoplasms / genetics
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Liver Neoplasms / immunology
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Liver Neoplasms / prevention & control
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Liver Neoplasms / secondary
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Lung Neoplasms / genetics
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Lung Neoplasms / immunology
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Lung Neoplasms / prevention & control
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Lung Neoplasms / secondary
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Lymphatic Metastasis
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Mammary Neoplasms, Experimental / genetics*
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Mammary Neoplasms, Experimental / immunology*
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Mammary Neoplasms, Experimental / pathology
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Mammary Neoplasms, Experimental / prevention & control
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Neoplasm Metastasis / genetics*
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Neoplasm Metastasis / immunology*
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Neoplasm Metastasis / pathology
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Neoplasm Metastasis / prevention & control
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STAT6 Transcription Factor
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T-Lymphocytes, Cytotoxic / pathology
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Trans-Activators / deficiency*
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Trans-Activators / genetics*
Substances
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STAT6 Transcription Factor
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Stat6 protein, mouse
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Trans-Activators