# Cellular and microenvironmental mechanisms linking aging to tumor control

> **NIH NIH K22** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $162,000

## Abstract

Project Summary.
Research. Cancer incidence increases dramatically with age. While the average life expectancy continues to
rise, one consequence is that cancer cases are predicted to grow by 45% between 2010 and 2030, highlighting
the critical need to study the intersection between aging physiology and tumorigenesis. However, the majority of
cancer research is performed using young adult mice as pre-clinical cancer models, where impact of
environmental risk factors, like aging, on key features of tumorigenesis cannot be measured. The immune
system is especially vulnerable to functional decline with aging. Many different kinds of immune cells can be
found infiltrating tumors, where CD8+ T cells in particular can identify and selectively kill cancer cells by
recognizing tumor features that differ from normal tissue. Although studies have shown that aging diminishes
CD8+ T cell proliferation and effector responses following bacterial and viral infections, the role of aging on anti-
tumor immunity is still a major black box. Based on our preliminary data in tumors from young and aged mice,
we hypothesize that impaired anti-tumor immunity by CD8+ T cells contributes to tumorigenesis during aging. To
test this hypothesis, Aim 1 will first develop mouse models to study aging, cancer, and anti-tumor immunity, and
then identify mechanisms that alter immune cell function in the tumor niche using flow cytometry and single cell
RNA-sequencing. In Aim 2, we will define metabolic changes in the aged tumor microenvironment and then test
whether these are causal for CD8+ T cell dysfunction. Finally, Aim 3 will determine whether enhancing metabolic
pathways in immune cells identified by transcriptomic and metabolomic analysis can improve tumor control
during aging. By revealing how the tumor microenvironment changes with age and the impact on anti-tumor
immunity, these studies will identify mechanisms that drive T cell dysfunction in tumors that may be targeted to
improve cancer prevention and therapy.
Candidate. Dr. Alison Ringel, PhD, is the PI for this research proposal. She has worked as a postdoctoral fellow
for the past five years at Harvard Medical School, where she has sought to understand the molecular
mechanisms that drive tumorigenesis in response to environmental cancer risk factors such as obesity. She is
in the process of interviewing for tenure-track faculty positions and has mapped out a detailed professional
development plan that will enable her to transition to an independent research career where she will develop her
research program on aging and tumorigenesis. She aims to become a leader in cancer immunology by applying
an innovative systems biology approach to dissect the tumor niche, which will distinguish her independent work
from that of her postdoctoral mentors. Her long-term goal is to lead an independent cancer research program
dedicated to the discovery of molecular mechanisms within tumors that regulate local immune responses and
tum...

## Key facts

- **NIH application ID:** 10890796
- **Project number:** 5K22CA266150-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Alison Epstein Ringel
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $162,000
- **Award type:** 5
- **Project period:** 2022-07-11 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890796

## Citation

> US National Institutes of Health, RePORTER application 10890796, Cellular and microenvironmental mechanisms linking aging to tumor control (5K22CA266150-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10890796. Licensed CC0.

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