Effects of the MHC Class II Transactivator on the Growth and Metastasis of Breast Tumors

摘要

I have finalized my research on the effects of the MHC class II transcriptional transactivator (CIITA) on the growth and metastasis of breast tumors. Mouse model systems have shown that CIITA expression, in and of itself, is at best not beneficial for tumor immunotherapy in the mouse model system. Surprisingly, even in the context of the immune costimulatory molecules CD8O (137-1) and CDB6 (137-2), CIITA was unable to mount and immune response in tumor challenged mice. When the system was modified to examine the ability of CIITA to induce immunogenicity of the tumor, it was found that CIITA was actually detrimental to survival. This result is not surprising considering that dogma in immunology states that engagement of the MHC-TCR complex without additional costimulation can lead to T cell anergy. What is surprising is that the classical costimulatory molecules CD8O and CD88 are unable to provide this T cell costimulation in the context of CIITA. Additional experiments have also been undertaken to examine novel CIITA genes induced by CIITA. These studies provide a wealth of useful information regarding proposed human cancer therapy trials utilizing CIITA.