Abstract
Cell-mediated adaptive immunity is very important in tumor immune surveillance and tumor vaccination. However, the genetic program underlying an effective adaptive antitumor immunity is elusive. T-bet and Eomesodermin (Eomes) have been suggested to be master regulators of Th1 cells and CD8(+) T cells. However, whether they are important for T cell-mediated antitumor immunity is controversial. In this paper, we show that the combined germline deletion of T-bet and T cell-specific deletion of Eomes resulted in profound defects in adaptive antitumor immune responses. T-bet and Eomes drive Tc1 differentiation by preventing alternative CD8(+) T cell differentiation to Tc17 or Tc2 cells. Surprisingly, T-bet and Eomes are not critical for the generation of systemic CTL activities against cancer cells. Instead, T-bet and Eomes are crucial for tumor infiltration by CD8(+) T cells. This study defines T-bet and Eomes as critical regulators of T cell-mediated immune responses against tumor.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / pathology
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Cancer Vaccines / administration & dosage
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Cancer Vaccines / therapeutic use
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Cell Line, Tumor
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Cells, Cultured
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Disease Models, Animal
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Hyaluronan Receptors / biosynthesis
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Lymphocytes, Tumor-Infiltrating / immunology
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Lymphocytes, Tumor-Infiltrating / metabolism
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Lymphocytes, Tumor-Infiltrating / pathology
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Melanoma, Experimental / immunology*
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Melanoma, Experimental / pathology
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Melanoma, Experimental / prevention & control*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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T-Box Domain Proteins / deficiency
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T-Box Domain Proteins / genetics
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T-Box Domain Proteins / physiology*
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism*
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T-Lymphocytes / pathology
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / pathology
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T-bet Transcription Factor
Substances
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Cancer Vaccines
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Cd44 protein, mouse
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Eomes protein, mouse
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Hyaluronan Receptors
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T-Box Domain Proteins
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T-bet Transcription Factor