Wednesday, January 28, 2026 1/28/2026

Towards Precision Immuno-Oncology: Unraveling the Genomic Determinants and Mechanisms Underlying Immunotherapy Efficacy and Resistance

Award Number: R35CA232097
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Towards Precision Immuno-Oncology: Unraveling the Genomic Determinants and Mechanisms Underlying Immunotherapy Efficacy and Resistance - PROJECT SUMMARY/ABSTRACT Title: Towards Precision Immuno-Oncology: Unraveling the Genomic Determinants and Mechanisms Underlying Immunotherapy Efficacy and Resistance Immunotherapy has shown considerable promise for improving outcomes for cancer patients. Treatment of patients with antibodies against CTLA4, PD-1, or PD-L1 can result in dramatic responses and durable tumor control in some patients. However, most patients do not benefit and ICB treatment can cause severe side effects. Therefore, it is of paramount importance in the field to understand the mechanisms underlying sensitivity and resistance to ICB and other immunotherapies. The long-term goal of our research program is to unravel the molecular mechanisms underlying sensitivity and resistance to immunotherapies such as ICB and to work towards a better understanding of how to use immunotherapy in a precise and individualized manner. We propose to investigate how tumor and patient genetics/genomics affect tumor immune phenotypes and influence the response and resistance to immunotherapies. Over the next 7 years, our efforts will be focused on addressing three important questions with clear mechanistic and translational relevance. First, we will undertake a comprehensive analysis of how the diversity of mutational landscapes and densities, and DNA damage repair (DDR) deficiencies affect immunotherapy response in cancers treated with ICB (anti-PD1 or anti-CTLA4). This is aimed at developing and credentialing a precise model for ICB sensitivity and resistance to allow the design of rationale therapeutic combinations and personalization of ICB treatment. Second, we will use pre-clinical models and patient samples to evaluate how driver mutations in critical DDR mutations influence tumor immunity, ICB response, and acquired resistance. Third, we will characterize how the patient germline genotype (HLA), together with somatic mutation profiles of tumors, influence response to ICB.


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 = -$1 )
2026	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	000	8	12/18/2025	NON-COMPETING CONTINUATION	-$1
														Subtotal = -$1

Issue Date FY: 2024 ( Subtotal = $961,680 )
2024	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	000	8	8/26/2024	NON-COMPETING CONTINUATION	$961,680
														Subtotal = $961,680

Issue Date FY: 2023 ( Subtotal = $992,049 )
2023	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	001	7	8/30/2023	NON-COMPETING CONTINUATION	$992,049
2023	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	000	6	1/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $992,049

Issue Date FY: 2022 ( Subtotal = $992,049 )
2022	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	001	6	9/26/2022	NON-COMPETING CONTINUATION	$81,351
2022	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	000	6	8/11/2022	NON-COMPETING CONTINUATION	$910,698
														Subtotal = $992,049

Issue Date FY: 2021 ( Subtotal = $865,728 )
2021	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	005	5	8/24/2021	NON-COMPETING CONTINUATION	$865,728
2021	2020	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	003	4	12/7/2020	SUPPLEMENT FOR EXPANSION	$0
2021	2020	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	004	4	8/5/2021	NON-COMPETING CONTINUATION	$0
2021	2020	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	002	4	12/4/2020	NON-COMPETING CONTINUATION	$0
2021	2019	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	001	3	10/27/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$147,128
2021	2019	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Treatment Research	000	2	10/27/2020	NON-COMPETING CONTINUATION	-$147,128
														Subtotal = $865,728

Issue Date FY: 2020 ( Subtotal = $1,194,264 )
2020	2020	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	003	4	9/18/2020	SUPPLEMENT FOR EXPANSION	$161,000
2020	2020	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	002	4	9/14/2020	NON-COMPETING CONTINUATION	$1,033,264
2020	2019	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cancer Treatment Research	001	3	9/2/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$193,694
2020	2019	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Treatment Research	000	2	9/2/2020	NON-COMPETING CONTINUATION	-$193,694
														Subtotal = $1,194,264

Issue Date FY: 2019 ( Subtotal = $992,237 )
2019	2019	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Treatment Research	000	2	8/9/2019	NON-COMPETING CONTINUATION	$992,237
														Subtotal = $992,237

Issue Date FY: 2018 ( Subtotal = $1,040,850 )
2018	2018	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Treatment Research	000	1	8/29/2018	NEW	$1,040,850
														Subtotal = $1,040,850

Grand Total All Awards = $7,038,856

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Towards Precision Immuno-Oncology: Unraveling the Genomic Determinants and Mechanisms Underlying Immunotherapy Efficacy and Resistance

Award Number: R35CA232097

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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