Factors contributing to T cell persistence in a tolerizing tumor environment

Cancer is a leading cause of death worldwide, accounting for at least 10% of all deaths globally. Current therapies for cancer include surgical excision, chemotherapy and immunotherapy. CD8[+] T cells are adaptive immune cells responsible for eradicating tumor cells. However, these T cells can be rendered ineffective through tolerance. Yet in various mouse models and human patients, tolerant T cells persist. The aim of this project is to identify factors that support T cell persistence in a tolerizing tumor environment. Using a spontaneous prostate cancer model, we study antigen-specific T cells that have been shown to be locally tolerant in the prostate tumor environment. In this thesis, I compare the immune response in normal, antigen bearing, tumor transgenic and tumor-antigen transgenic mouse models. Results show that T cell infiltration and persistence in the tolerizing prostate environment is dependent on the presence of antigen and tumorigenic/tumor-related factors. Although antigen-specific T cells are locally tolerant in the prostate of tumor-antigen transgenic mice, they generally persist in the prostates of tumor transgenic mice regardless of whether antigen is present or not. Further analyses revealed that T cells infiltrate the prostate and can proliferate extensively in the tolerizing tumor environment due to the presence of antigen. Interestingly, antigen-specific T cells are depleted from the spleens of mice that express antigen in their prostates.

Department dc:contributor.department

Harvard University--MIT Division of Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2010

Author dc:creator

• Olurinde, Mobolaji O

Advisor dc:contributor.advisor

• Jianzhu Chen.

• Harvard University--MIT Division of Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/58180

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/58180