Morder, Kristin
(2023)
Changes in the Gut Microbiome After Cancer Treatment: Are We Setting Patients Back Before They Begin?
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Colorectal cancer (CRC) is a deadly cancer that is becoming more commonly diagnosed in younger patients. One major issue with CRC is that it is largely unresponsive to new immunotherapies, such as PD-1 checkpoint inhibitor blockade. Individuals with microsatellite instability high (MSI-H) and mismatch repair deficiencies (dMMR) seem to be the only ones that have tumors that respond to PD-1, but this only accounts for about 10% of all CRC cases. The other 90% of patients who do not have these types of tumors will have no response to PD-1 therapy. Research has shown that the microbiome is involved with the regulation of the immune system, with previous results from patients who have received PD-1 found that patients who responded well had a more diverse microbiome compared to those who did not respond. Results from our mouse model show that groups who received chemotherapy in the form of 5-flurouracil along with anti-PD1 antibody had a lower tumor clearance rate compared to the anti-PD1 alone group, as well as the broad-spectrum antibiotics and anti-PD1 group. When looking at the tumors from these mice, flow cytometry analysis showed that mice who received 5-flurouracil along with anti-PD1 treatment had significantly increased numbers of CD8+ T cells that secreted higher levels of interferon gamma (IFNg). The anti-PD1 alone group had a large population of CD8+ T cells in the tumor that were double positive for IFNg and tumor necrosis alpha (TNFa). These results support that traditional cancer treatments, like chemotherapy, may lead to gut dysbiosis that changes how the immune system reacts to cancer in a patient and decrease the efficacy of anti-PD1 treatment. It raises the question of how to proceed with treatments if the traditional ones that are currently used can hurt a person’s ability to respond to immunotherapy.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
11 May 2023 |
| Date Type: |
Publication |
| Defense Date: |
19 April 2023 |
| Approval Date: |
11 May 2023 |
| Submission Date: |
27 April 2023 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
49 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
colorectal cancer, immunotherapy |
| Date Deposited: |
11 May 2023 16:07 |
| Last Modified: |
11 May 2023 16:07 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/44775 |
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