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.
Antigenic Cancer Cells Grow Progressively in Immune Hosts without Evidence for T Cell Exhaustion or Systemic Anergy
Address correspondence to Maresa Wick, The University of Chicago, Department of Pathology, 5841 S. Maryland Ave., MC 1089, Chicago, Illinois 60637. Phone: 773-702-9214; FAX: 773-702-3701; E-mail: [email protected]
M. Wick and P. Dubey contributed equally to this paper.
Part of this work was presented in abstract form at the Keystone Symposia “Cellular Immunology and the Immunotherapy of Cancer III,” Copper Mountain, February 1997.
Abbreviations used in this paper: α-KGDH, α-ketoglutarate dehydrogenase; BES, N,N-bis[2-hydroxyethyl]-2-aminoethanesulfonic acid; CDMEM, DMEM containing 10% FCS; CTL, cytolytic T lymphocyte(s); MLTC, mixed lymphocyte–tumor cell culture; rhIL-2, recombinant human IL-2; rmIL-2, recombinant murine IL-2.
Maresa Wick, Purnima Dubey, Hartmut Koeppen, Christopher T. Siegel, Patrick E. Fields, Lieping Chen, Jeffrey A. Bluestone, Hans Schreiber; Antigenic Cancer Cells Grow Progressively in Immune Hosts without Evidence for T Cell Exhaustion or Systemic Anergy. J Exp Med 21 July 1997; 186 (2): 229–238. doi: https://doi.org/10.1084/jem.186.2.229
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