# Targeting macrophages to reduce colorectal cancer: Impact of metabolic reprogramming

> **NIH NIH K00** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $98,812

## Abstract

PROJECT SUMMARY
Colorectal Cancer (CRC) is the third-most common malignancy for men or women. There are a number of
known risk factors associated with CRC including inflammatory bowel diseases, diet, and obesity with the
underlying cause behind these risk factors being chronic low grade inflammation. Additionally, epidemiological
research has convincingly shown that obesity increases colorectal cancer (CRC) risk, with generally stronger
associations observed in men than in women, suggesting that sex hormones may play a role. Macrophages
(MΦs) are a major player in the inflammatory response and are not only the most abundant immune population
in a tumor microenvironment but also are a driving force in obesity-associated inflammation leading to
metabolic dysfunction. While it is well established that macrophages can be primary contributors to protumoral
processes, their mechanism for promoting tumor growth throughout various stages of CRC is not clear. In
addition sex differences in the role of macrophages during obesity driven CRC is severely understudied. I am
proposing to elucidate the role of MΦs in CRC and obesity, and further, the interaction between MΦs, obesity,
and sex differences in CRC (F99 phase). Understanding the role of MΦs and their mechanism of action in
metabolic dysfunction and the progression of CRC will translate to the development of more effective
prevention/treatment approaches. My data indicates that depleting macrophages in late stage CRC can
decrease tumor number and macrophage associated inflammation in the colon. Additionally, I report that
reducing macrophages following diet induced insulin resistance does not ameliorate metabolic function and
may result in anemia and neutrophilia, contrary to previous reports. I also expect to uncover unique
macrophage behaviors with in sex specific and/or obesity driven CRC.
Emerging evidence identifies macrophage metabolism as a promising target for therapeutic intervention in
cancer and other inflammatory diseases. Tumor associated macrophages (TAM) can represent up to 50% of a
tumor mass and are correlated with poor prognosis. Despite the dominating presence of TAMs in the cancer
state, their phenotype and metabolic profiles remain unclear; thus, highlighting the need for more specific
approaches for characterizing the heterogeneous TAMs populations. Additionally, TAMs exhibit a unique
metabolism and have the ability to reprogram their metabolic phenotype to survive depending on their
environment. There is promising evidence that manipulation of glycolysis or fatty acid oxidation can reprogram
TAMs toward an antitumor phenotype and provide a unique strategy for cancer immunotherapy. The goal of
the K00 phase is to uncover the mechanisms linking TAM metabolism to cancer progression so that
therapeutic targets can be developed.

## Key facts

- **NIH application ID:** 10456764
- **Project number:** 5K00CA234920-06
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jackie Bader
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $98,812
- **Award type:** 5
- **Project period:** 2018-09-14 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456764

## Citation

> US National Institutes of Health, RePORTER application 10456764, Targeting macrophages to reduce colorectal cancer: Impact of metabolic reprogramming (5K00CA234920-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10456764. Licensed CC0.

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