In studying the immune response to cancer, we have discovered a novel murine T cell subset which expresses an alpha beta T cell receptor (TCR)/CD3 complex, but unlike the majority of peripheral T cells, has neither a CD4 or CD8 accessory molecule. In addition, this cell expresses the antigen NK1, previously thought to be found exclusively on thymus independent, alpha beta TCR negative natural killer cells. Cancer cells are known to often down regulate the level of MHC class I molecules on their surface in an apparent attempt to evade immune detection. Mice challenged with an MHC class I low tumor which has been transfected to produce the lymphokine IL-2, respond with an accumulation of these cells at the challenge site. In vitro, NK1+TCR+alpha beta+ T cells can be demonstrated to have cytolytic activity against the wild type tumor when taken from animals primed with the transfectant. The experiments proposed here seek to explore the function of NK1+TCRalpha beta+ T cells in the antitumor immune response. Specifically, the signals required for cell recognition and activation will be examined, with particular attention to target cell class I MHC down regulation, utilizing MHC gene transfection of class I low tumors to dissect the role of these molecules in the nature of the cellular response. The events leading to the selection of this subset during thymic development will also be studied. The environment where this will be carried out is a laboratory with a primary interest in molecular and cellular immunology, with a particular focus on studying the antitumor immune response. There is considerable experience in the field of thymic development and T cell function. The oncology center is a multidisciplinary cancer institute with a strong commitment to developing immunotherapy as a major treatment modality. My training in clinical medicine and oncology followed by two years of basic investigation in immunology has given me an appreciation of the potential for utilizing the immune response to cancer in the treatment of patients. Only by discovering the basic principles underlying the way in which tumors evade the immune system, can a rational approach be taken to successfully modify this response.
| Levitsky, H I; Montgomery, J; Ahmadzadeh, M et al. (1996) Immunization with granulocyte-macrophage colony-stimulating factor-transduced, but not B7-1-transduced, lymphoma cells primes idiotype-specific T cells and generates potent systemic antitumor immunity. J Immunol 156:3858-65 |
| Levitsky, H I; Lazenby, A; Hayashi, R J et al. (1994) In vivo priming of two distinct antitumor effector populations: the role of MHC class I expression. J Exp Med 179:1215-24 |
