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Investigating the Spatial Dynamics of Intratumoral Immune Cells in Breast Cancer

Award Number: F30CA260950
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 06/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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Investigating the Spatial Dynamics of Intratumoral Immune Cells in Breast Cancer - PROJECT ABSTRACT While immunotherapy has revolutionized the treatment of certain malignancies it has yet to yield the same results in breast cancer. This is striking, given that there is an abundance of intra-tumoral immune cells that affect disease outcomes. Evidence suggests that these leukocytes are strategically positioned to execute their functions and yet little is known about their spatial dynamics over tumor progression and regression. I aim to detail a comprehensive and mechanistic picture of these spatiotemporal dynamics using recent advances in high-dimensional in situ imaging. I hypothesize that as tumors progress, immunosuppressive cells will block immune cell organizational structures and cell-cell communications that promote antitumor immunity and that this phenotype will be reversed upon tumor regression. This will be assessed by characterizing the spatial organization, cell-cell interactions, activation/inhibition markers, and cytokine production of the main leukocyte lineages in situ over disease course. My preliminary data demonstrate that I can identify most of these major immune cell types at once within breast tumors, including subsets of macrophages, dendritic cells, and T cells. In addition, I found that two subsets of macrophages have differential localization: one which is intra-tumoral and another that is almost exclusively peritumoral. This peritumoral macrophage population closely interacts with T regulatory cells, which are important for immunosuppression in breast cancer. As such, I hypothesize that peritumoral FDMs spatially organize to interact with T regulatory cells via TCR-MHC II, thereby activating Tregs and skewing tumors toward an immunosuppressed microenvironment. To test this, I will use genetic mouse models to deplete these populations in a tumor stage-specific manner and assess the impact on tumor growth, survival, and response to clinical therapies. Overall, this proposal aims to understand the spatial dynamics of leukocytes in breast cancer, which will reveal key cell-cell interactions, organizational structures, and cellular communication networks that need to be disrupted/promoted in order to reengage antitumor immunity, facilitating the development of effective immunotherapies.


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: 2027 ( Subtotal = $1 )
2027	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cancer Research Manpower	000	2	10/22/2026	NON-COMPETING CONTINUATION	$1
														Subtotal = $1

Issue Date FY: 2026 ( Subtotal = -$53,005 )
2026	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cancer Research Manpower	001	3	1/27/2026	NON-COMPETING CONTINUATION	-$44,566
2026	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cancer Research Manpower	000	2	1/27/2026	NON-COMPETING CONTINUATION	-$8,439
														Subtotal = -$53,005

Issue Date FY: 2024 ( Subtotal = $44,566 )
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cancer Research Manpower	000	3	7/9/2024	NON-COMPETING CONTINUATION	$44,566
														Subtotal = $44,566

Issue Date FY: 2023 ( Subtotal = $52,694 )
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cancer Research Manpower	000	2	5/31/2023	NON-COMPETING CONTINUATION	$52,694
														Subtotal = $52,694

Issue Date FY: 2022 ( Subtotal = $51,752 )
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cancer Research Manpower	002	1	8/5/2022	NEW	$716
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cancer Research Manpower	000	1	2/22/2022	NEW	$51,036
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cancer Research Manpower	001	1	2/22/2022	NEW	$0
														Subtotal = $51,752

Grand Total All Awards = $96,008

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Investigating the Spatial Dynamics of Intratumoral Immune Cells in Breast Cancer

Award Number: F30CA260950

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 06/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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