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.
Zhu
Yibei
Y
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Ju
Songguang
S
Chen
Elizabeth
E
Dai
Shao
S
Li
Changyou
C
Morel
Penelope
P
Liu
Lin
L
Zhang
Xueguang
X
Lu
Binfeng
B
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D000098815:T-bet Transcription Factor
D019496:Cancer Vaccines; C476399:Cd44 protein, mouse; C491198:Eomes protein, mouse; D018960:Hyaluronan Receptors; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor