Antigenic cancer cells grow progressively in immune hosts without evidence for T cell exhaustion or systemic anergy.
One enigma in tumor immunology is why animals bearing malignant grafts can reject normal grafts that express the same nonself-antigen. An explanation for this phenomenon could be that different T cell clones react to the normal graft and the malignant cells, respectively, and only the tumor-reactive clonotypes may be affected by the growing tumor. To test this hypothesis, we used a T cell receptor transgenic mouse in which essentially all CD8(+) T cells are specific for a closely related set of self-peptides presented on the MHC class I molecule Ld. We find that the tumor expressed Ld in the T cell receptor transgenic mice but grew, while the Ld-positive skin was rejected. Thus, despite an abundance of antigen-specific T cells, the malignant tissue grew while normal tissue expressing the same epitopes was rejected. Therefore, systemic T cell exhaustion or anergy was not responsible for the growth of the antigenic cancer cells. Expression of costimulatory molecules on the tumor cells after transfection and preimmunization by full-thickness skin grafts was required for rejection of a subsequent tumor challenge, but there was no detectable effect of active immunization once the tumor was established. Thus, the failure of established tumors to attract and activate tumor-specific T cells at the tumor site may be a major obstacle for preventive or therapeutic vaccination against antigenic cancer.
Wick
M
M
Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA. mwick@midway.uchicago.edu
Dubey
P
P
Koeppen
H
H
Siegel
C T
CT
Fields
P E
PE
Chen
L
L
Bluestone
J A
JA
Schreiber
H
H
D000818:Animals; D006084:Graft Rejection; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D007108:Immune Tolerance; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell