T-bet and eomesodermin are required for T cell-mediated antitumor immune responses

Yibei Zhu ¹, Songguang Ju , Elizabeth Chen , Shao Dai , Changyou Li , Penelope Morel , Lin Liu , Xueguang Zhang , Binfeng Lu

Affiliations

¹ Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

PMID: 20713880
83 citations

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.

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Full text on Journal of immunology (Baltimore, Md. : 1950)

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