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Delineating the mechanisms by which tumor immunity multicellular networks shape T cell state

Award Number: K08CA273547
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/23/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Delineating the mechanisms by which tumor immunity multicellular networks shape T cell state - T cells are greatly impacted by their environment, interacting with neighboring cells that may attract, stimulate, inhibit, and otherwise alter T cell activity. Examining multicellular tissue organization is thus required for unraveling the T cell anti-tumor response. Yet, little is known about what multicellular networks exist in cancer, how they are organized, and how they modulate T cell activity. This project explores the mechanistic basis of a tumor immunity multicellular network (hub) discovered in the candidate’s (Dr. Jonathan Chen) recent single cell transcriptomic study of human colorectal cancer. The objective of this proposal is to investigate the composition, spatial organization and function of this immunity hub in relation to the anti-tumor T cell response. This proposal aims to (1) spatially map cellular interactions in the immunity hub that may shape T cell behavior and (2) identify environmental factors in the immunity hub shaping CXCL13+ CD8 T cell state and uncover the role of CXCL13 in CRC. The candidate anticipates these studies will demonstrate that the newly discovered tumor immunity multicellular network recruits tumor-specific T cells, and that multiple cell types within the hub participate in shaping the state of these T cells. Furthermore, this investigation of the immunity hub is likely to identify promising strategies for therapeutic manipulation. The candidate, Dr. Jonathan Chen, is currently a postdoc in the lab of Dr. Nir Hacohen and an Instructor in the Department of Pathology of the Massachusetts General Hospital. The proposal incorporates specific technical skills that will be required for the project, including training in analysis of ultra-highplex RNA in situ hybridization datasets. The structured career development plan includes training and mentorship in laboratory management, scientific leadership, research communication, grant writing, and other critical career skills. These technical and career skills will be acquired under the guidance of Dr. Nir Hacohen, who will serve as primary mentor and has a history of trainees obtaining faculty positions in academia, and Dr. Eli Van Allen as computational co-mentor. A Research Advisory Committee of world-class scientists including Drs. Arlene Sharpe, David Rimm, and David Ting will provide additional support and guidance. Through this comprehensive program, the candidate will acquire a unique set of research skills that will enable him to transition to an independent physician-scientist faculty position with a lab focused on basic mechanisms and therapeutic opportunities in cancer immunology.


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 Research Manpower	000	3	12/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $226,554 )
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Research Manpower	001	3	8/25/2025	NON-COMPETING CONTINUATION	$226,554
2025	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	000	1	2/28/2025	NEW	$0
														Subtotal = $226,554

Issue Date FY: 2024 ( Subtotal = $226,554 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Research Manpower	001	2	9/12/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$226,554
2024	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	000	1	9/12/2024	NEW	$0
														Subtotal = $226,554

Issue Date FY: 2023 ( Subtotal = $226,554 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	000	1	8/23/2023	NEW	$226,554
														Subtotal = $226,554

Grand Total All Awards = $679,662

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Delineating the mechanisms by which tumor immunity multicellular networks shape T cell state

Award Number: K08CA273547

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/23/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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