The biology of human invariant natural killer T cells and regulatory T cells in allogeneic hematopoietic stem cell transplantation
Abstract/Contents
- Abstract
- Allogeneic hematopoietic stem cell transplant (HSCT) can be used as a curative treatment for patients with hematologic malignancies; however, acute graft-versus-host disease (aGVHD) is a highly inflammatory disease and a major complication that can occur following this therapy. Two populations capable of regulating immune responses are invariant natural killer T (iNKT) and regulatory T (Treg) cells, but their biology in the clinical aGVHD setting is not fully understood. Thus, I examined how iNKT and Treg cells regulate aGVHD in the clinical setting. To study human iNKT cells, I used a high-dimensional, data-driven approach to devise a framework for parsing human iNKT cell heterogeneity. A population of iNKT cells characterized by HLA-DR expression was found to be enriched in aGVHD patients and associated with exhaustion markers and a Th1 profile, suggesting a loss of immunoregulatory mechanisms in aGVHD. This phenotype, along with other discovered phenotypic markers, were also associated with aGVHD outcomes, suggesting that iNKT cells can potentially serve as a biomarker and therapeutic target in allogeneic HSCT. Beyond these potential clinical implications, a new framework was discovered for understanding human iNKT cell heterogeneity that advances our knowledge of human iNKT cell biology. As our understanding of fundamental human Treg cell biology is more advanced, a phase I/II study of the infusion of Treg cells with hematopoietic stem cells to prevent aGVHD in adult patients undergoing myeloablative allogeneic HSCT for hematological malignancies has been started and is ongoing. Clinically, greater than grade II aGVHD was noted in two patients in the first cohort of five patients who received cryopreserved Treg cells. In a second cohort of seven patients who received fresh Treg cells and single agent aGVHD prophylaxis, none developed aGVHD. A key finding is that patients in the second cohort showed immune reconstitution comparable to patients who underwent allogeneic HSCT on standard-of-care. Together, these studies reveal new insights into the biology of human iNKT and Treg cells in the clinical aGVHD setting.
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 | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Xie, Bryan Jiaming |
|---|---|
| Degree supervisor | Meyer, Everett |
| Degree supervisor | Negrin, Robert S |
| Thesis advisor | Meyer, Everett |
| Thesis advisor | Negrin, Robert S |
| Thesis advisor | Davis, Mark M |
| Thesis advisor | Gentles, Andrew |
| Thesis advisor | Maecker, Holden |
| Degree committee member | Davis, Mark M |
| Degree committee member | Gentles, Andrew |
| Degree committee member | Maecker, Holden |
| Associated with | Stanford University, Program in Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Bryan Jiaming Xie. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/hg504vm8131 |
Access conditions
- Copyright
- © 2021 by Bryan Jiaming Xie
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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