# Targeting myeloid cells to increase efficacy of immunotherapy against brain tumors.

> **NIH NIH K08** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $211,464

## Abstract

PROJECT SUMMARY
The proposed research career development program seeks to investigate the mechanism by
which myeloid cells in brain tumors become immunosuppressive, preventing the immune system
from controlling the tumor even in the presence of immunotherapy designed to activate it. The
candidate is currently a Research Fellow in the Department of Pathology of the Massachusetts
General Hospital. The proposal incorporates specific technical skills that will be required for the
project including training in immune biology and advanced immune assay techniques. The
structured career development plan includes training and mentorship in laboratory management,
scientific leadership, research communications, grant writing, and other critical career skills.
These technical and career skills will be acquired under the guidance of Dr. Bradley Bernstein,
who will serve as primary mentor and has a history of trainees that obtain group leader positions
in academia, as well as a Research Advisory Committee of word-class scientists including Drs.
Mario Suva, John Iafrate, and Nir Hacohen. Through this comprehensive program, the candidate
will acquire a unique set of clinical and research skills that will enable him to transition to an
independent physician scientist faculty position with a lab focused on basic mechanisms and
therapeutic opportunities in brain cancer epigenetics and immunology.
The research strategy will investigate immunosuppressive tumor-associated myeloid cells in brain
tumors – where they come from, the epigenetic mechanism by which they become
immunosuppressive, and how to potentially transform them. Transforming or selectively killing
myeloid cells that express immunosuppressive programs offers great opportunity to sensitize
brain tumors to immunotherapy. However, it remains unknown if these myeloid cells come from
circulating monocytes or endogenous microglia, or what make them immunosuppressive,
significantly hindering the design of rational clinical strategies to target these cells in brain tumors.
The aims of this proposal are to: (1) Determine the origin of immunosuppressive myeloid cell
states in brain tumors, (2) identify the epigenetic regulatory factors that maintain the
immunosuppressive cell program, (3) discover perturbations that eliminate or transform
immunosuppressive myeloid cells. Overall, these studies will provide valuable data needed to
develop targeted therapies against immunosuppressive myeloid cells and increase the efficacy
of immunotherapy for brain cancer patients.

## Key facts

- **NIH application ID:** 11144745
- **Project number:** 7K08CA276819-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Tyler Eugene Miller
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $211,464
- **Award type:** 7
- **Project period:** 2023-07-19 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11144745

## Citation

> US National Institutes of Health, RePORTER application 11144745, Targeting myeloid cells to increase efficacy of immunotherapy against brain tumors. (7K08CA276819-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11144745. Licensed CC0.

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