|
|
|
|
|
|
|
||
By
From the * Department of Pathology, 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.
Department of Surgery, and § Ben May Institute for Cancer
Research, The University of Chicago, Chicago, Illinois 60637; and the 
Bristol-Myers Squibb
Pharmaceutical Research Institute, Seattle, Washington 98121
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
