Antigenic cancer cells grow progressively in immune hosts without evidence for T cell exhaustion or systemic anergy

Maresa Wick, Purnima Dubey, Hartmut Koeppen, Christopher T. Siegel, Patrick E. Fields, Lieping Chen, Jeffrey A. Bluestone, Hans Schreiber

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)229-238
Number of pages10
JournalJournal of Experimental Medicine
Volume186
Issue number2
DOIs
StatePublished - Jul 21 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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