Neutrophils eradicate tumors via reactive oxygen species in response to immunotherapy
Abstract/Contents
- Abstract
- Although neutrophils are powerful cytotoxic cells capable of killing microbes and injuring host tissues, they are often associated with tumor-promoting inflammation and immunosuppression rather than tumor killing. We demonstrate here that neutrophils can be therapeutically harnessed to eradicate tumors. Following intratumoral co-administration of tumor-binding antibodies, CD40 agonist, and tumor necrosis factor, neutrophils rapidly infiltrate tumors and mediate tumor clearance. This is accomplished through an inflammatory cascade wherein complement activation induces leukotriene B4 (LTB4) production, which in turn activates neutrophil-dependent reactive oxygen species (ROS) production via xanthine oxidase (XO), ultimately resulting in tumor cell death and induction of adaptive anti-tumor immunity. This is interrupted by selective blockade of complement, LTB4, XO, or by scavenging ROS, indicating a necessary role for each of these elements. These results demonstrate the therapeutic capacity of neutrophils to mediate tumor-eradicating immunity and define a mechanism of tumor clearance with multiple promising targets for therapeutic intervention.
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 | Linde, Ian Lisle |
|---|---|
| Degree supervisor | Engleman, Edgar G |
| Thesis advisor | Engleman, Edgar G |
| Thesis advisor | Davis, Mark M |
| Thesis advisor | Sunwoo, John B |
| Thesis advisor | Winslow, Monte |
| Degree committee member | Davis, Mark M |
| Degree committee member | Sunwoo, John B |
| Degree committee member | Winslow, Monte |
| Associated with | Stanford University, Program in Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Ian Linde. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/mt842sf8643 |
Access conditions
- Copyright
- © 2021 by Ian Lisle Linde
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