# Investigating the Spatial Dynamics of Intratumoral Immune Cells in Breast Cancer

> **NIH NIH F30** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $44,566

## Abstract

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.

## Key facts

- **NIH application ID:** 10853124
- **Project number:** 5F30CA260950-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Joseph Anthony Saglimbeni
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $44,566
- **Award type:** 5
- **Project period:** 2022-06-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10853124

## Citation

> US National Institutes of Health, RePORTER application 10853124, Investigating the Spatial Dynamics of Intratumoral Immune Cells in Breast Cancer (5F30CA260950-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10853124. Licensed CC0.

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