# Targeting M2-Tumor Associated Macrophages to overcome tumor immunity in metastatic castration-resistant prostate cancer

> **NIH NIH K22** · JOHNS HOPKINS UNIVERSITY · 2020 · $153,640

## Abstract

Prostate cancer (PCa) is deadly once it metastasizes and continues to be an unmet medical need here in the
United States. Increasing evidence has demonstrated that the prostate tumor microenvironment which,
surrounds the cancer cells, significantly contributes to its progression, circumvention of current therapies,
resistance to newer immune checkpoint therapies, and its survival. Using clinical samples, the principal
investigator has found that the tumor microenvironment of metastatic castration-resistant prostate cancer
(mCRPC) is infused with reactive stroma enriched with M2 macrophages known as M2-tumor-associated
macrophages (M2-TAMs). His previous studies have partly elucidated how M2-TAMs and reactive stroma
associate with primary and metastatic disease, identified five new surface-enriched markers on M2-TAMs, and
has helped demonstrate that M2-TAMs are key regulators of PCa epithelial-to-mesenchymal transition (EMT)
and tumorigenesis. Therefore, the need to design targeted therapies that target M2-TAMs within the tumor
microenvironment is sorely needed. Other studies have demonstrated the importance of M2-TAMs in
angiogenesis, metastasis, and their dependence on glutamine metabolism. Based on his data and that of other
groups, the principal investigator hypothesizes that M2-TAMs are ideal therapeutic targets in mCRPC and help
confer mCRPC resistant to immunotherapy. This proposal will determine novel M2-TAM marker expression in
mCRPC (Specific Aim 1) and assess if the elimination of M2-TAMs in prostate cancer can reverse mCRPC
immunotherapy resistance (Specific Aims 2, 3). This will be the first body of work using syngeneic mCRPC tumor
models treated with either anti-CD206 peptide (RP182) or a novel glutamine antagonist, JHU083 followed by
immunotherapy and a comprehensive immunological analysis of the tumor microenvironment. The principal
investigator will also learn new techniques necessary to accomplish the proposed research under the advisement
team (Drs. Drake, McConkey, Pardoll, Pienta, and Powell) and his pathologist consultant (Dr. De Marzo) all of
whom have pioneering expertise in PCa biology, mCRPC treatment, cancer metabolism, single-cell RNA
sequencing, and cancer immunotherapy. Importantly, his advisory committee collectively has a very strong track
record of training both clinical and postdoctoral fellows who have been successful in transitioning into
independent investigators at top tier research institutions. He will also engage in and present at national
seminars, take coursework on laboratory biostatistics, cancer metabolism and immuno-metabolism, single cell
RNA-sequencing, Jr. Faculty leadership program, grant-writing seminars, and training on running a laboratory.
Combining these new skills learned during the K22 award period with his prior training in cancer biology and
cancer immunology, will ensure a strong technical foundation to launch an independent laboratory dissecting
and targeting innate immune cells and the...

## Key facts

- **NIH application ID:** 9921343
- **Project number:** 5K22CA237623-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jelani Chinelo Zarif
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $153,640
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9921343

## Citation

> US National Institutes of Health, RePORTER application 9921343, Targeting M2-Tumor Associated Macrophages to overcome tumor immunity in metastatic castration-resistant prostate cancer (5K22CA237623-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9921343. Licensed CC0.

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