The Role of Lymph Node Subcapsular Sinus Macrophages in Limiting Tumor Progression through a B-cell Response
Date
2019-07-10
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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.
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Keywords
Lymph Node, Subcapsular Sinus, Lymphatics, Cancer, B-cell, Macrophages, Immunology, Immunotherapy
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.