Thursday, February 19, 2026 2/19/2026

Role of microbiota in therapy to ovarian cancer

Award Number: R01CA216234
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/10/2017
PERIOD OF PERFORMANCE END DATE: 03/31/2023

Group Awards By:

View Award Description

Role of microbiota in therapy to ovarian cancer - This proposal is submitted in response to the RFA, “Research answers to NCI's provocative questions”, in particular, question 10, which asks, How do microbiota affect the response to cancer therapies? Our preliminary data show that when tumor cells colonize the omentum, a fatty tissue in the peritoneal cavity, they trigger a profound Treg-mediated tolerogenic response that prevents tumor-specific CD8 T cells from clearing the tumor. Interestingly, this activity is specific for the omentum and involves a subset of Tregs known as visceral-adipose tissue (VAT)-associated Tregs. VAT-associated Tregs uniquely express the transcription factor PPARg and also express the ST2 component of the IL-33 receptor on their surface. These cells are found exclusively in adipose tisses and are not found in conventional lymhoid organs (like the spleen and lymph nodes) and are not found in peripheral sites. Importantly, VAT-associated Tregs are found in the omentum, which is the site of ovarian cancer metastasis. In additioin to showing that VAT-associated Tregs profoundly impair immunity to tumors that colonize the omentum, we also found that this activity is completely dependent on gut microbiota. As a result, VAT-associated Treg activity is impaired and anti-tumor immunity is restored in the omenta of germ-free mice. These results are surprising, since published data show that microbiota promote (rather than prevent) the anti-tumor effect of chemotherapy. These results were explained by the ability of chemotherapy to compromise the gut epithelium, allowing the translocation of microbiota and thereby triggering an IL-17 response, which facilitates the effects of chemotherapy on the clearance of tumors. Based on these data, the central hypothesis of this proposal is that the microbiota play opposing roles in promoting the immune suppressive Tregs under steady state conditions and by promoting the immune stimulatory Th17 responses following chemotherapy. Moreover, these types of responses are location dependent, with VAT-associated Tregs residing and responding primarily in fatty tissues like the omentum. Thus, therapy for ovarian cancer, which routinely metastasizes to the omentum, may have different outcomes than therapy to tumors in other locations. The experiments in this application test this hypothesis using a spontaneous mouse model of ovarian cancer and determine the mechanistic links between the gut microbiota and immunity in the peritoneal cavity using and ectopic model of ovarian cancer.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	5	12/21/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $426,139 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	5	2/23/2021	NON-COMPETING CONTINUATION	$426,139
														Subtotal = $426,139

Issue Date FY: 2020 ( Subtotal = $426,139 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	4	2/27/2020	NON-COMPETING CONTINUATION	$426,139
														Subtotal = $426,139

Issue Date FY: 2019 ( Subtotal = $413,353 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	3	3/21/2019	NON-COMPETING CONTINUATION	$413,353
														Subtotal = $413,353

Issue Date FY: 2018 ( Subtotal = $426,139 )
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	001	2	5/23/2018	NON-COMPETING CONTINUATION	$42,616
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	2	2/19/2018	NON-COMPETING CONTINUATION	$383,523
														Subtotal = $426,139

Issue Date FY: 2017 ( Subtotal = $426,139 )
2017	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	1	4/10/2017	NEW	$421,834
2017	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	001	1	4/25/2017	NEW	$4,305
														Subtotal = $426,139

Grand Total All Awards = $2,117,909

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of microbiota in therapy to ovarian cancer

Award Number: R01CA216234

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/10/2017

PERIOD OF PERFORMANCE END DATE: 03/31/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer