Viral infections can cause severe diseases in mammals, especially human being, however recently studies showed that some type of viral infection could help tumor patients to control the tumor growth. Understanding the mechanisms how immune system combat against viral infection and using viruses against lethal diseases such as cancer could help to develop better treatment therapies and vaccines to treat patients. In this thesis, we have investigated the role of cell adhesion molecule (CEACAM1) in LCMV infection and how LCMV influences tumor growth in tumor-bearing mice.
Here in this study, we demonstrated that murine carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) antibody promote T cells response during lymphocytic choriomeningitis virus (LCMV) infection. Human CEACAM1 antibody enhance Human T cell function in vitro. This study clearly showed that CEACAM1 antibody could improve T cell response in mouse and human.
In another set of experiments, we investigated the role of virus infection in the B16F10-OVA model. We found tumor-specific CD8+ T cells homed into tumors, and hardly react against the tumor cells. Reason for unresponsiveness against the tumor was a strong down-regulation of MHC-I in an advanced tumor. Innate immune activation by LCMV restored the MHC class I expression, enhanced T cell function and led to tumor regression. This investigation shows that growing tumor cells do not necessarily lead to systemic exhaustion of the anti-tumoral CD8+ T cell response. Lack of innate signals is an additional reason for limited CD8+ T cell mediated cytotoxicity against the tumor. In conclusion, these two studies elucidate the functional role of CEACAM1 antibody during viral infection, and the role of immune activation by LCMV in tumor-bearing mice.
|Advisor:||Lang , Karl|
|School:||Universitaet Duisburg-Essen (Germany)|
|Source:||DAI-C 82/8(E), Dissertation Abstracts International|
|Subjects:||Virology, Oncology, Immunology, Molecular biology|
|Keywords:||Cell adhesion molecules, Tumor growth, Viral infections|
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