# Targeting the Epigenome to Improve Responses to Immunotherapy

> **NIH NIH K00** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $101,101

## Abstract

Project Summary
Conventional dendritic cells (cDCs) are central regulators of the adaptive immune response, and have been
shown to be required for the induction of T cell-mediated anti-tumor immunity. In particular, a subset of cDCs
(cDC1) is responsible for transporting tumor antigens to the lymph node and cross presenting antigen in order
to activate cytotoxic T lymphocytes, thereby inducing an anti-tumor response. We have recently observed TIM-
3 (T-cell immunoglobulin and mucin domain containing-3) expression on cDCs in human and murine mammary
tumors, and found that TIM-3 blockade improved response to standard-of-care paclitaxel chemotherapy in
models of triple-negative and luminal B disease. This occurred through increased chemokine expression by
cDCs, without a corresponding in T cell infiltration, leading me to hypothesize that the spatial localization of
cDCs and T cells within tumors is a critical determinant of successfully immunotherapy. In the F99 portion of
this application I will therefore seek to determine if TIM-3 blockade alters the spatial organization of T cells, and
if this is responsible for therapeutic efficacy. In the K00 phase of this proposal I will expand these studies to
evaluate whether cDC/T cell clustering is a prerequisite for response to immune checkpoint blockade and other
therapeutic modalities.

## Key facts

- **NIH application ID:** 10767837
- **Project number:** 5K00CA245807-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** ALYCIA GARDNER
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $101,101
- **Award type:** 5
- **Project period:** 2019-09-06 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767837

## Citation

> US National Institutes of Health, RePORTER application 10767837, Targeting the Epigenome to Improve Responses to Immunotherapy (5K00CA245807-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10767837. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*