Myeloid cells in cancer progression and cancer treatment
Abstract/Contents
- Abstract
- The importance of the immune system in cancer and cancer therapy has become firmly established over the last decade. Current treatments have great potential, but remain ineffective for many patients and tumor types. Much of the work in cancer immunotherapy has focused on components of the adaptive immune system. Thus, the impact of innate immune components, including myeloid cells, on cancer immunotherapy is poorly understood and not well-utilized with current cancer therapies. Myeloid cells are a major subset of innate immune cells that are known to modulate immune behavior to generate pro- or anti-tumor environments in mechanisms that are both dependent upon and independent of the adaptive immune system. The work described here is a collection of projects investigating several aspects of the myeloid cell compartment in various tumor models. First, we found that retinoic acid deficiency in intestinal tissue was critical in the process of intestinal tumor growth and development. Pharmacologic correction of this retinoic acid deficit leads to reduction of tumor number and size, while diet-induced exacerbation of the deficit leads to increased tumor number and size. These findings correlate with the capacity of intestinal dendritic cells from the lamina propria to induce CD4 T cells of the inflammatory Th17 phenotype or regulatory T cell. Additional lines of experiments focused on the unmet clinical need for intestinal tumor detection tools. We report development of novel fluorescent probe for cathepsins, a frequent tumor-associated protein product of myeloid cells, which facilitates robust detection of both mouse and human intestinal tumors. In another line of experiments, we investigated the signaling pathways important in licensing bone marrow dendritic cells to internalize tumor cell-IgG antibody immune complexes and to stimulate potent anti-tumor T cell responses. Namely, alterations in SHP-1 activity and the PI3K/Akt pathway were identified as major checkpoints of dendritic cell immunostimulatory function. Finally, we investigate the essential innate immune components of tumor-binding antibody immunotherapy in established B16 melanoma tumors. Neutrophils are necessary for clearance of established B16 tumors via a complement cascade- and reactive oxygen species-dependent mechanism. The immunotherapeutic approach studied here demonstrates the complex interactions of the innate immune system underlying tumor clearance via a mechanism requiring neutrophils, complement and iron-dependent reactive oxygen species.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Prestwood, Tyler Ryan |
|---|---|
| Degree supervisor | Engleman, Edgar G |
| Thesis advisor | Engleman, Edgar G |
| Thesis advisor | Alizadeh, Ash |
| Thesis advisor | Shizuru, Judith Anne |
| Degree committee member | Alizadeh, Ash |
| Degree committee member | Shizuru, Judith Anne |
| Associated with | Stanford University, Program in Stem Cell Biology and Regenerative Medicine. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Tyler Ryan Prestwood. |
|---|---|
| Note | Submitted to the Program in Stem Cell Biology and Regenerative Medicine. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Tyler Prestwood
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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