# Interrogating the role for ATP-dependent chromatin remodeling complexes in immune response

> **NIH NIH F30** · HARVARD MEDICAL SCHOOL · 2022 · $51,752

## Abstract

PROJECT SUMMARY / ABSTRACT
Desipte the marked clinical success of treating cancer with immunotherapies, including anti-PD-1, anti-CTLA-4
and anti-PD-L1, the majority of patients do not respond to these treatments or relapse following initial
response. Research efforts to analyze the role of tumor cell intrinsic mechanisms that mediate responsiveness
to immunotherapy treatments offer great potential to improve these treatment strategies. One layer of cell
intrinsic regulation that remains to be thorughly analyzed is the epigenetic profile of tumor cells and how this
level of regulation impacts the overall responsiveness to immunotherapy. Epigenetic regulation can be
achieved by the structural remodelling of the chromatin by distinct complexes such as the mammalian
Switch/Sucrose Non-Fermentable (mSWI/SNF) ATP-dependent chromatin remodelling complex. mSWI/SNF
uses energy generated from ATP-hydrolysis to alter chromatin through many mechanisms including ejection,
destabilisation and restructuring of nucleosomes allowing for changes in the accessibility of distinct genetic
regions resulting in context specific, highly regulated gene expression. The mSWI/SNF complex is of particular
interest because data from an in vivo CRISPR screen in B16 melanoma demonstrated that deletion of genes
encoding select subunits of the mSWI/SNF each conferred resistance to anti-PD-1 treatment (Manguso et. al,
2017). Through this proposal we will conduct a comprehensive analysis of all mSWI/SNF subunits to determine
their role in regulating responsiveness of melanoma to anti-PD-1 immunotherapy, and deeply interrogate the
mechanistic role of both conformations of mSWI/SNF, BAF and PBAF, in melanoma by analyzing the genomic
location of these complexes, changes in chromatin accessiblity and the resulting transcriptomic changes which
impact cellular processes. As a whole, this proposal offers great potential to impact the fundamental
understanding of SWI/SNF biology as well as inform our understanding of epigenetic regulation as it relates to
immunotherapy responsiveness.

## Key facts

- **NIH application ID:** 10375502
- **Project number:** 5F30CA239317-04
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Dawn E Comstock
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375502

## Citation

> US National Institutes of Health, RePORTER application 10375502, Interrogating the role for ATP-dependent chromatin remodeling complexes in immune response (5F30CA239317-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10375502. Licensed CC0.

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