T-bet and Eomesodermin Are Required for T Cell-Mediated Antitumor Immune Responses

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. The Journal of Immunology, 2010, 185: 3174-3183.