Striking immunodominance hierarchy of naturally occurring CD8+ and CD4+ T cell responses to tumor antigen NY-ESO-1.
Immunodominance has been well-demonstrated in many antiviral and antibacterial systems, but much less so in the setting of immune responses against cancer. Tumor Ag-specific CD8+ T cells keep cancer cells in check via immunosurveillance and shape tumor development through immunoediting. Because most tumor Ags are self Ags, the breadth and depth of antitumor immune responses have not been well-appreciated. To design and develop antitumor vaccines, it is important to understand the immunodominance hierarchy and its underlying mechanisms, and to identify the most immunodominant tumor Ag-specific T cells. We have comprehensively analyzed spontaneous cellular immune responses of one individual and show that multiple tumor Ags are targeted by the patient's immune system, especially the "cancer-testis" tumor Ag NY-ESO-1. The pattern of anti-NY-ESO-1 T cell responses in this patient closely resembles the classical broad yet hierarchical antiviral immunity and was confirmed in a second subject.
Jackson
Heather
H
Ludwig Institute for Cancer Research, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia.
Dimopoulos
Nektaria
N
Mifsud
Nicole A
NA
Tai
Tsin Yee
TY
Chen
Qiyuan
Q
Svobodova
Suzanne
S
Browning
Judy
J
Luescher
Immanuel
I
Stockert
Lisa
L
Old
Lloyd J
LJ
Davis
Ian D
ID
Cebon
Jonathan
J
Chen
Weisan
W