Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective anti-tumor T cell response
Abstract/Contents
- Abstract
- Mobilization of the T cell response against cancer has the potential to achieve long-lasting cures. However, it is not known how to optimally harness antigen presenting cells to achieve an effective anti-tumor T cell response. In this study, we show that anti-CD47 antibody-mediated phagocytosis of cancer by macrophages can initiate an anti-tumor T cell immune response. Using the ovalbumin model antigen system, anti-CD47 antibody-mediated phagocytosis of cancer cells by macrophages resulted in increased priming of OT-I T cells (CD8+), but did not prime OT-II T cells (CD4+). The CD4+ T cell response was characterized by a reduction in Foxp3+ regulatory T cells. Macrophages following anti-CD47-mediated phagocytosis primed CD8+ T cells to exhibit cytotoxic effector function in vivo, protecting animals from tumor challenge. We conclude that anti-CD47 antibody treatment not only enables macrophage phagocytosis of cancer, but can also initiate an anti-tumor cytotoxic T cell immune response. Anti-CD47-mediated phagocytosis of cancer cells by macrophages leads to priming of a predominant CD8+ T cell response without priming of CD4+ T cells, demonstrating differential priming of T cell responses by macrophages. Priming of effector CD8+ T cells is difficult to achieve with existing vaccines for cancer and infectious diseases. Anti-CD47-based vaccination strategies serve as a promising new strategy for overcoming this challenge for treating or preventing human disease.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2013 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Tseng, Diane | |
|---|---|---|
| Associated with | Stanford University, Department of Cancer Biology. | |
| Primary advisor | Weissman, Irving L | |
| Thesis advisor | Weissman, Irving L | |
| Thesis advisor | Davis, Mark M | |
| Thesis advisor | Engleman, Edgar G | |
| Thesis advisor | Levy, Ronald, 1941 December 6- | |
| Advisor | Davis, Mark M | |
| Advisor | Engleman, Edgar G | |
| Advisor | Levy, Ronald, 1941 December 6- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Diane Tseng. |
|---|---|
| Note | Submitted to Program in Cancer Biology. |
| Thesis | Ph.D. Stanford University 2013 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2013 by Diane Tseng
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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