Cutting edge: STAT6-deficient mice have enhanced tumor immunity to primary and metastatic mammary carcinoma.
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.
Ostrand-Rosenberg
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Department of Biological Sciences, University of Maryland, Baltimore, MD 21250, USA. srosenbe@umbc.edu
Grusby
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MJ
Clements
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VK
D000818:Animals; D019046:Bone Marrow Neoplasms / Q000235:genetics / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018450:Disease Progression; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D008207:Lymphatic Metastasis; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D050800:STAT6 Transcription Factor; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics*
D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators