TY - JOUR
T1 - Antigenic cancer cells grow progressively in immune hosts without evidence for T cell exhaustion or systemic anergy
AU - Wick, Maresa
AU - Dubey, Purnima
AU - Koeppen, Hartmut
AU - Siegel, Christopher T.
AU - Fields, Patrick E.
AU - Chen, Lieping
AU - Bluestone, Jeffrey A.
AU - Schreiber, Hans
PY - 1997/7/21
Y1 - 1997/7/21
N2 - 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 L(d). We find that the tumor expressed L(d) in the T cell receptor transgenic mice but grew, while the L(d)-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.
AB - 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 L(d). We find that the tumor expressed L(d) in the T cell receptor transgenic mice but grew, while the L(d)-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.
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U2 - 10.1084/jem.186.2.229
DO - 10.1084/jem.186.2.229
M3 - Article
C2 - 9221752
AN - SCOPUS:0030807565
SN - 0022-1007
VL - 186
SP - 229
EP - 238
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -