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The Center for Tumor-Immune Systems Biology at MSKCC

Award Number: U54CA274492
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/16/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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The Center for Tumor-Immune Systems Biology at MSKCC - The Center for Tumor-Immune Systems Biology at MSKCC SUMMARY The advent of cancer immunotherapies based on immune checkpoint blockade (ICB) has revolutionized clinical care in multiple solid tumor types and demonstrated the power of the immune system to target and eliminate cancer cells. Despite these breakthroughs, the efficacy of ICB-based immunotherapy is limited to a subset of cancers, and even in tumors where ICB is now the standard of care, only a fraction of patients achieve durable complete responses. Addressing these limitations requires (1) improving our fundamental understanding of tumor-immune interactions in immunological contexts where current immunotherapies fail and (2) developing novel strategies for enhancing responses in contexts where they have only partial success. The Center for Tumor-Immune Systems Biology at MSKCC has assembled a multi-disciplinary team of leading investigators in computational biology, immunology, and cancer biology to tackle these challenges. The Center is organized around three Research Projects that integrate computational and experimental studies in mouse models and molecular analyses in patient tumors in both immunotherapy-resistant and -responsive contexts, exploiting novel machine learning modeling of single-cell multiome, highly multiplexed optical imaging using confocal immunofluorescence, and spatial transcriptomic data sets. We will investigate distinct immune microenvironments where cancers are refractory to ICB: metastatic colonization of the brain, an immune- privileged organ where the interplay of cancer cells, astrocytes, and different states of disease-associated microglia dictate modes of invasion (Project I); and mismatch-repair proficient primary colon cancer, where tumors reside in a tolerizing microenvironment and interact with complex cellular circuits of regulatory and conventional T cells, together with metastases to the lymph node and liver (Project II). We will also carry out a systems biology interrogation of cancer cell death mechanisms in models of ICB-responsive melanoma and renal cell carcinoma, based on findings that engineering mitochondrial damage-dependent but caspase- independent cell death elicits anti-cancer immunity and protection against tumor rechallenge (Project III). A Shared Resource Core will interact with all three Research Projects to develop computational methods and establish technologies for spatial analyses of the tumor-immune microenvironment. These studies will advance our fundamental understanding of tumor-immune ecosystems in ICB-refractory microenvironments and of immune responses to therapeutically induced immunogenic cancer cell death in ICB-responsive settings, ultimately leading to novel immunotherapeutic targets and combination strategies. Our team will build on the successes of our previous CSBC U54 Center award for the Center for Cancer Systems Immunology at MSKCC, which produced numerous high-impact studies at the forefront of systems biology and cancer immunology. Our Research Center will also carry out innovative outreach and training activities to disseminate research findings in tumor-immune systems biology and to train young scientists in this critical field.


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	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	001	4	2/26/2026	NON-COMPETING CONTINUATION	$0
2026	2025	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	000	4	2/13/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $2,654,999 )
2025	2025	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	002	4	9/11/2025	NON-COMPETING CONTINUATION	$2,654,999
2025	2024	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	000	3	4/14/2025	NON-COMPETING CONTINUATION	$0
2025	2024	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	001	3	5/19/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,654,999

Issue Date FY: 2024 ( Subtotal = $2,698,250 )
2024	2024	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	001	3	8/22/2024	NON-COMPETING CONTINUATION	$2,522,250
2024	2024	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	002	3	9/4/2024	SUPPLEMENT FOR EXPANSION	$176,000
2024	2023	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	000	2	6/3/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,698,250

Issue Date FY: 2023 ( Subtotal = $2,601,900 )
2023	2023	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	000	2	8/22/2023	NON-COMPETING CONTINUATION	$2,601,900
														Subtotal = $2,601,900

Issue Date FY: 2022 ( Subtotal = $2,655,000 )
2022	2022	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	000	1	9/16/2022	NEW	$2,655,000
														Subtotal = $2,655,000

Grand Total All Awards = $10,610,149

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The Center for Tumor-Immune Systems Biology at MSKCC

Award Number: U54CA274492

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/16/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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