Modeling organism-wide immunity in health and cancer
Abstract/Contents
- Abstract
- Immune cells function in an interacting hierarchy that coordinates activities of various cell types according to genetic and environmental contexts. We developed graphical approaches to construct an extensible immune reference map from mass cytometry data of cells from different organs, incorporating landmark cell populations as flags on the map to compare cells from distinct samples. The maps recapitulated canonical cellular phenotypes and revealed reproducible, tissue-specific deviations. The approach revealed influences of genetic variation and circadian rhythms on immune system structure, enabled direct comparisons of murine and human blood cell phenotypes, and even enabled archival fluorescence-based flow cytometry data to be mapped onto the reference framework. This foundational reference map provides a working definition of systemic immune organization to which new data can be integrated to reveal deviations driven by genetics, environment, or pathology. We have further extended this concept to initiate a framework for modeling human immunity, using whole peripheral blood samples as an inaugural dataset. Moreover, we demonstrate that this method is capable of modeling the effects of immunotherapeutic interventions on immune responses across the system. We have recently developed novel strategies for inducing anti-tumor immune responses that leverage the stimulatory capacity of tumor-binding antibodies. When combined with adjuvants to activated dendritic cells, this combination therapy is capable of inducing sterilizing immunity in a number of translatable and autochthonous animal models as well as in primary cells from cancer patients in culture. Using these therapies as a model of an effective anti-tumor immune response, our system-wide modeling approach revealed the systemic events resulting in the eradication of spontaneous breast tumors.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Spitzer, Matthew H | |
|---|---|---|
| Associated with | Stanford University, Department of Immunology. | |
| Primary advisor | Engleman, Edgar G | |
| Primary advisor | Nolan, Garry P | |
| Thesis advisor | Engleman, Edgar G | |
| Thesis advisor | Nolan, Garry P | |
| Thesis advisor | Davis, Mark | |
| Thesis advisor | Khavari, Paul A | |
| Thesis advisor | Levy, Ronald, 1941 December 6- | |
| Advisor | Davis, Mark | |
| Advisor | Khavari, Paul A | |
| Advisor | Levy, Ronald, 1941 December 6- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Matthew H. Spitzer. |
|---|---|
| Note | Submitted to the Department of Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Matthew Hunt Spitzer
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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