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A deubiquitination module controls Treg adaptation to tumor microenvironment

Award Number: R01CA257520
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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A deubiquitination module controls Treg adaptation to tumor microenvironment - Project Summary: One of the recent advances in cancer treatment is the development of immunotherapy largely through targeting the checkpoint receptors. However, attempts at immunotherapy to increase antitumor immune responses have achieved very limited success. A major hurdle in tumor immunotherapy is mediated by regulatory T (Treg) cells, which suppress the function of antitumor effector T cells. The lineage transcription factor Forkhead Box P3 (FoxP3) is known as a programmer for Treg adaptation in the harsh tumor microenvironment such as metabolic changes and hypoxia. However, the factors that control FoxP3-mediated Treg fitness to orchestrate the survival and functions of intratumoral Treg cells have not been identified. Importantly, our recent publications and preliminary discoveries in the current application suggest that tumor microenvironment factors possibly induce Treg fitness/adaptation through selectively upregulating a deubiquitinase module, including USP21 and USP22, but not USP7, of FoxP3 to control Treg adaptation. The current proposed studies will identify the tumor microenvironment factors that induce USP21 and USP22 expression in Tregs (Aim 1), and to test whether Tregs with simultaneous USP21 and USP22 deletion fail to adapt in the harsh tumor microenvironment, which consequently potentiates the antitumor immune therapy (Aim 2). Results from our proposed study will define a novel molecular cue in control Treg fitness to the tumor microenvironment and provide a rationale for the combined USP21 and USP22 suppression in antitumor immune therapy.


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 = $0 )
2026	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	000	5	11/13/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $560,370 )
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	001	5	7/8/2025	NON-COMPETING CONTINUATION	$56,036
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	000	5	12/4/2024	NON-COMPETING CONTINUATION	$504,334
														Subtotal = $560,370

Issue Date FY: 2024 ( Subtotal = $533,802 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	001	4	4/16/2024	NON-COMPETING CONTINUATION	$28,092
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	000	4	11/27/2023	NON-COMPETING CONTINUATION	$505,710
														Subtotal = $533,802

Issue Date FY: 2023 ( Subtotal = $552,115 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	000	3	1/26/2023	NON-COMPETING CONTINUATION	$552,115
														Subtotal = $552,115

Issue Date FY: 2022 ( Subtotal = $553,526 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	001	2	4/28/2022	NON-COMPETING CONTINUATION	$45,186
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	000	2	12/30/2021	NON-COMPETING CONTINUATION	$508,340
														Subtotal = $553,526

Issue Date FY: 2021 ( Subtotal = $561,629 )
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	000	1	12/21/2020	NEW	$561,629
														Subtotal = $561,629

Grand Total All Awards = $2,761,442

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A deubiquitination module controls Treg adaptation to tumor microenvironment

Award Number: R01CA257520

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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