Boosting macrophage appetites for cancer immunotherapy
Abstract/Contents
- Abstract
- Recent progress in the field of cancer immunotherapy has demonstrated the potential for harnessing the innate immune system in order to effectively treat cancers. Macrophages are an especially attractive target for cancer immunotherapy, as they are abundant in the vast majority of tumors and are capable of detecting and directly clearing cancer cells through phagocytosis. However, recent work has demonstrated that cancer cells are capable of evading clearance by macrophages within tumors by overexpressing innate immune checkpoint molecules called "don't eat me" signals. The prototypical "don't eat me" signal, CD47, is a surface protein expressed highly in many cancers, and monoclonal antibodies targeting the CD47 innate immune checkpoint have demonstrated great clinical promise, and even cures, in hematologic malignancies including myelodysplastic syndromes and AML. Despite these successes, CD47 blockade does not promote complete phagocytosis in all types of cancers, which suggests the presence of additional "don't eat me" signals. Through this work we have identified two previously-unknown innate immune checkpoints that exist between macrophages and cancer cells, MHC class I:LILRB1 and CD24:Siglec- 10, and we demonstrate the therapeutic promise of blocking these novel "don't eat me" signals in order to maximize macrophage function, reduce cancer growth, and extend survival in vivo. Collectively, this work suggests a new paradigm that innate immune checkpoints are redundant and employed in a tissue-specific and even tumor-specific manner, and makes clear the need to measure the collective expression of these "don't eat me" signals in order to optimize patient responses to both innate and adaptive immunotherapies
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 | Barkal, Amira |
|---|---|
| Degree supervisor | Weissman, Irving L |
| Thesis advisor | Weissman, Irving L |
| Thesis advisor | Jaiswal, Sidd |
| Thesis advisor | Majeti, Ravindra, 1972- |
| Degree committee member | Jaiswal, Sidd |
| Degree committee member | Majeti, Ravindra, 1972- |
| Associated with | Stanford University, Program in Stem Cell Biology and Regenerative Medicine |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Amira Barkal |
|---|---|
| Note | Submitted to the Program in Stem Cell Biology and Regenerative Medicine |
| Thesis | Thesis Ph.D. Stanford University 2021 |
| Location | https://purl.stanford.edu/bt667fw0636 |
Access conditions
- Copyright
- © 2021 by Amira Barkal
- License
- This work is licensed under a Creative Commons Attribution Non Commercial No Derivatives 3.0 Unported license (CC BY-NC-ND).
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