Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Metabolic Control of Innate and Adaptive Immunity in Breast Cancer

Award Number: R01CA237149
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/11/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2027

Group Awards By:

View Award Description

Metabolic Control of Innate and Adaptive Immunity in Breast Cancer - PROJECT SUMMARY/ABSTRACT Immunotherapy is a promising approach for treating patients with advanced breast cancer. However, immunosuppressive microenvironments induced by regulatory T cells (Treg) present a major barrier to successful anti-tumor immunotherapy. Defining the suppressive mechanisms used by different types of tumor- infiltrating Treg cells is essential for the development of novel strategies to treat human breast cancer. We recently discovered high percentages of γδ Treg cells existing among the tumor-infiltrating lymphocytes (TILs) of breast tumor patients, which are strongly negatively correlated with clinical outcomes. We further identified a novel suppressive mechanism whereby γδ Treg cells induce senescence in T cells and dendritic cells (DCs) that then also develop potent suppressive activity. Therefore, it is critical to further identify the molecular mechanisms responsible for γδ Treg-induced senescence in immune cells, and then to develop strategies to reverse senescence induction mediated by γδ Treg cells. Increasing evidence indicates that the ability of a lymphocyte to perform functional immune responses is controlled by pathways of energy metabolism. However, little is known about the regulation of energy metabolism in tolerogenic DCs and Treg cells. We recently found that γδ Treg cells dramatically reprogram DC lipid metabolism. In addition, we observed that TLR8 signaling significantly suppresses glucose metabolism in human γδ Treg cells via inhibition of both glucose transporters and glycolysis-related enzymes. The central hypotheses of this proposal are that: 1) breast cancer-derived γδ Treg cells rewrite lipid metabolism in DCs, resulting in DC senescence with tolerogenic phenotypes and functions; 2) reprogramming of metabolism in Treg cells and DCs can serve as a novel strategy to synergistically enhance anti-tumor immunity for tumor immunotherapy. Specific Aim 1 seeks to identify what lipid species are changed in γδ Treg-induced senescent DCs and whether the altered lipid components are causatively related to the DC senescence and impaired functions. We will then investigate the importance of transcription factor STAT and PD1-PDL1 signaling in controlling lipid metabolism disorder, senescence induction and impaired functions occurred in γδ Treg-treated DCs. Specific Aim 2 will identify the key glucose metabolites that involve γδ Treg-mediated immune suppression and are regulated by TLR8 signaling for functional reversal in human γδ Treg cells. We will then test the novel concept that TLR8 activation in γδ Treg cells combined with checkpoint blockade of PD-L1 in DCs can serve as novel strategies to reprogram their metabolism and synergistically enhance anti-tumor immunity for breast cancer immunotherapy. A positive outcome from these studies should lead to novel strategies to reprogram innate and adaptive immune cell metabolism for future breast cancer immunotherapy.


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: 2026 ( Subtotal = $420,182 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Detection and Diagnosis Research	000	6	1/23/2026	NON-COMPETING CONTINUATION	$378,164
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Detection and Diagnosis Research	001	6	4/16/2026	NON-COMPETING CONTINUATION	$42,018
														Subtotal = $420,182

Issue Date FY: 2024 ( Subtotal = $1 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Cancer Detection and Diagnosis Research	004	5	2/29/2024	NON-COMPETING CONTINUATION	$1
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Cancer Detection and Diagnosis Research	005	5	4/16/2024	NON-COMPETING CONTINUATION	$0
2024	2023	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Detection and Diagnosis Research	003	4	2/9/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$424,338
2024	2022	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Cancer Detection and Diagnosis Research	002	3	2/9/2024	NON-COMPETING CONTINUATION	-$422,302
2024	2022	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Cancer Detection and Diagnosis Research	000	3	2/2/2024	NON-COMPETING CONTINUATION	$0
2024	2021	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Cancer Detection and Diagnosis Research	001	2	2/9/2024	NON-COMPETING CONTINUATION	-$2,036
														Subtotal = $1

Issue Date FY: 2023 ( Subtotal = $433,609 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Detection and Diagnosis Research	001	4	9/7/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$433,609
2023	2022	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Cancer Detection and Diagnosis Research	000	3	9/7/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $433,609

Issue Date FY: 2022 ( Subtotal = $422,302 )
2022	2022	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Cancer Detection and Diagnosis Research	001	3	6/8/2022	NON-COMPETING CONTINUATION	$34,474
2022	2022	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Cancer Detection and Diagnosis Research	000	3	1/6/2022	NON-COMPETING CONTINUATION	$387,828
														Subtotal = $422,302

Issue Date FY: 2021 ( Subtotal = $93,461 )
2021	2021	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Cancer Detection and Diagnosis Research	000	2	2/4/2021	NON-COMPETING CONTINUATION	$93,461
														Subtotal = $93,461

Issue Date FY: 2020 ( Subtotal = $346,556 )
2020	2020	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Cancer Detection and Diagnosis Research	000	1	2/11/2020	NEW	$346,556
														Subtotal = $346,556

Grand Total All Awards = $1,716,111

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Metabolic Control of Innate and Adaptive Immunity in Breast Cancer

Award Number: R01CA237149

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/11/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer