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CUTTING EDGE |
*
Department of Biological Sciences, University of Maryland, Baltimore, MD 21250; and
Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Department of Medicine, Harvard Medical School, Boston, MA 02115
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.
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