The Role of Lymph Node Subcapsular Sinus Macrophages in Limiting Tumor Progression through a B-cell Response

Louie, Dante Alexander Patrick

The Role of Lymph Node Subcapsular Sinus Macrophages in Limiting Tumor Progression through a B-cell Response

dc.contributor.advisor	Liao, Shan
dc.contributor.advisor	von der Weid, Pierre Yves
dc.contributor.author	Louie, Dante Alexander Patrick
dc.contributor.committeemember	Mahoney, Douglas J.
dc.contributor.committeemember	Yipp, Bryan G.
dc.date	2019-11
dc.date.accessioned	2019-07-12T17:48:10Z
dc.date.available	2019-07-12T17:48:10Z
dc.date.issued	2019-07-10
dc.description.abstract	Cancer immunotherapy targeting antitumor T-cells is demonstrated to be promising in treating several types of cancers. Adoptive T-cell transfer and immune checkpoint inhibitors are among the most successful immunotherapies today. However, these therapies are not effective in all patients and they can lead to devastating side effects in patients, including autoimmune diseases such as colitis. A better understanding of different aspects of cancer immunity can reveal additional targets for optimal cancer immunotherapy. One of these aspects is the tumor-draining lymph node - the first lymphoid organ that encounters tumor-derived antigens and generates the first wave of anti-tumor immunity. Recent publications have revealed that the activation of B-cells suppresses tumor growth in melanoma mice models. In my studies, using a C57BL/6 syngeneic E0771 breast cancer cell line, tumor-derived antigens were detected in the germinal center with CD169+ subcapsular sinus macrophage in the tumor-draining lymph node. The importance of B-cells was demonstrated by using B-cell deficient mice, which significantly suppressed tumor growth compared to wild-type mice. Transferring wild-type B-cells to B-cell deficient mice recovered tumor growth. To determine if subcapsular sinus macrophages regulate B-cell activity, I depleted the lymph node subcapsular sinus macrophages with clodronate liposomes. Tumor growth and germinal center formation were increased when in the macrophage-depleted tumor-draining lymph nodes, suggesting subcapsular sinus macrophages limit B-cell activation in the lymph node. Collectively, my results reveal subcapsular sinus macrophages limit B-cell activity to prevent tumor growth, which can be a potential target for future cancer immunotherapy development.	en_US
dc.identifier.citation	Louie, D. A. P. (2019). The Role of Lymph Node Subcapsular Sinus Macrophages in Limiting Tumor Progression through a B-cell Response (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/36736
dc.identifier.uri	http://hdl.handle.net/1880/110621
dc.language.iso	eng	en_US
dc.publisher.faculty	Cumming School of Medicine	en_US
dc.publisher.institution	University of Calgary	en
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.	en_US
dc.subject	Lymph Node	en_US
dc.subject	Subcapsular Sinus	en_US
dc.subject	Lymphatics	en_US
dc.subject	Cancer	en_US
dc.subject	B-cell	en_US
dc.subject	Macrophages	en_US
dc.subject	Immunology	en_US
dc.subject	Immunotherapy	en_US
dc.subject.classification	Immunology	en_US
dc.title	The Role of Lymph Node Subcapsular Sinus Macrophages in Limiting Tumor Progression through a B-cell Response	en_US
dc.type	master thesis	en_US
thesis.degree.discipline	Medicine – Microbiology & Infectious Diseases	en_US
thesis.degree.grantor	University of Calgary	en_US
thesis.degree.name	Master of Science (MSc)	en_US
ucalgary.item.requestcopy	true	en_US