# Immunometabolic and epigenetic effects of obesity on innate immune surveillance in cancer

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $433,542

## Abstract

Project Summary
Obesity has reached epidemic proportions globally with the biggest heath and economic burden
being the many obesity-related diseases. Among these diseases, obesity is a strong risk factor for
cancer, accounting for up to 49% of certain cancers. It is expected that obesity will soon replace
smoking as the leading preventable cause of cancer. Despite increased public awareness and
prevention strategies, the prevalence of obesity and related diseases continue. Therefore there is
increased urgency to understand the pathways whereby obesity leads to other diseases, and to
develop new strategies prevent their progression.
It is now appreciated that obesity is associated with immune dysregulation, which may be the cause
of some obesity related diseases. Natural killer (NK) cells are so-called due to their natural
cytotoxicity against tumors cells. We have previously shown that obese individuals have reduced NK
cell numbers and the remaining NK cells are unable to kill tumors cells efficiently. The key
unanswered questions are 1) how does obesity induce NK cell defects, 2) Does NK cell impairment
increase the risk of cancer in obesity, and 3) Can obesity induced immune dysfunction be reversed or
prevented. This project will use a multi-disciplinary approach to decipher if epigenetic and metabolic
changes in NK cells in obesity lead to their inability to survey and kill tumors.
Immunometabolism is rapidly becoming an area of huge potential for treating disease, however much
is still to be discovered. Results from this project will yield new insight into the complex changes that
occur in innate immune cells in obesity and how they affect immune surveillance. It will also reveal a
largely unexplored intersection between metabolic pathways and epigenetic modifications in the
immune system. Our preliminary data shows that the effect of obesity is analogous to rapamycin
treatment in terms of the effect on dampening NK cell functions. This likely impacts the ability of the
innate immune system to act upon foreign or damaged cells when they encounter them, and may at
least partly explain the increased risk of infection and cancer in obese individuals.

## Key facts

- **NIH application ID:** 10265752
- **Project number:** 3R01AI134861-04S1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Lydia Lynch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $433,542
- **Award type:** 3
- **Project period:** 2020-08-28 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10265752

## Citation

> US National Institutes of Health, RePORTER application 10265752, Immunometabolic and epigenetic effects of obesity on innate immune surveillance in cancer (3R01AI134861-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10265752. Licensed CC0.

---

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