# (PQ3) Cellular and Molecular Mechanisms Driving Myeloid Compartment Variation in Human Triple Negative Breast Cancer

> **NIH NIH R01** · JACKSON LABORATORY · 2020 · $670,182

## Abstract

PROJECT SUMMARY
Numerous studies over the past decade examined the tumor and blood compartment in cancer patients. These
studies have added to our understanding of immune alterations in cancer, but have failed to fully explain the
functional variation in myeloid antigen presenting cells (mAPCs). We must address this gap before we can
begin to fully answer the question posed above because mAPCs control cancer antigen presentation to T cells
thereby launching and regulating anti-cancer immunity. The overarching goal of this proposal is to better
understand the molecular basis of variation in the immune response to triple negative breast cancer (TNBC) at
single cell level. This approach will likely redefine the biology of mAPCs in cancer. We propose a systematic
exploration of immune status in blood and tumors in a cohort of 75 TNBC patients with residual cancer. We
hypothesize that the variation in transcriptome and function of mAPCs in TNBC patients is linked with specific
genomic profiles of their associated cancer cells and contributes to variable response to chemotherapy and
disease progression. We propose two specific aims: In Aim 1, we will apply single cell transcriptomics to
identify myeloid APC-specific transcriptional profiles in the blood. We will do so at steady state and in response
to ex vivo activation with tumor derived factors. This will identify distinct transcriptomics and functional modules
that could enable prediction of cell behavior when tumor environments are altered. Gene sets and/or cells
defined in blood studies will be applied to tumors to trace these cells using mass spectrometry-based imaging
and to examine transcriptional profiles specific to leukocyte infiltrate harvested with macro dissection. In Aim 2,
we will examine genes that could be linked with the attraction and differentiation of APCs in the tumor
(chemokines and cytokines). We will examine links between cancer genomic aberrations and transcriptional
variation in APCs and between the ex vivo response of myeloid APCs to tumor products and in situ
transcriptional profiles. We will examine TNBC patient derived xenograft (PDX) tissues established from
residual disease to determine cancer-cell intrinsic chemokine/cytokine profiles, and their role in the attraction of
myeloid cells when implanted in humanized mice. CRISPR/Cas9 editing will be applied to cancer cells to
generate variants and to verify links with the variation in the APCs compartment and impact on tumor
progression and metastasis. These studies will lay a foundation for better understanding how immune
variations contribute to the aggressiveness of TNBC and enable the identification of potential actionable
therapeutic targets in residual disease.

## Key facts

- **NIH application ID:** 9972865
- **Project number:** 5R01CA219880-04
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Anna Karolina Palucka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $670,182
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972865

## Citation

> US National Institutes of Health, RePORTER application 9972865, (PQ3) Cellular and Molecular Mechanisms Driving Myeloid Compartment Variation in Human Triple Negative Breast Cancer (5R01CA219880-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9972865. Licensed CC0.

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