# Aging and the Ovarian Tumor Microenvironment

> **NIH NIH U01** · UNIVERSITY OF NOTRE DAME · 2020 · $115,875

## Abstract

ABSTRACT:
This project proposes to develop a new Partnership for Aging and Cancer Research by bringing together NIH
extra-mural and intra-mural investigators to collaboratively evaluate aging and the ovarian cancer (OvCa)
microenvironment. Advanced age is a significant risk factor for OvCa incidence and negatively affects survival.
We have demonstrated that immune system dysregulation is associated with aging, reflected by both
increased myelopoiesis and decreased lymphopoiesis, such that immune cells exhibiting exhausted and over
activated phenotypes are enhanced in aging. Additionally age-related changes in plasma exosome
concentration and content differentially alter B cell activation. Furthermore, our pre-clinical studies have shown
that aged mice develop consistently greater peritoneal tumor burden relative to young cohorts with concomitant
changes in tumor immune cell composition and that pro-inflammatory signaling supports a pro-metastatic
phenotype. Proposed experiments will test the hypothesis that host aging promotes OvCa metastatic
progression through changes in the peritoneal proteome and through dysregulation of the peritoneal immune
landscape. To address this hypothesis, Aim 1 will characterize age-related changes in the proteome
(secreted, cell surface and intracellular) of tumor-naïve primary peritoneal mesothelial cells, examine age-
associated alterations in the ascites proteome of tumor-bearing young vs aged mice, and assess the functional
consequences of ascites-derived exosome-mediated information transfer to tumor cells and host peritoneal
mesothelium. Complementary experiments in Aim 2 will characterize changes in the immune landscape of
both host and tumor tissues in young vs aged mice, examine the contribution of aging peritoneal B1a
lymphocytes to OvCa growth and assess the role of ascites-derived exosome-mediated information transfer to
alterations in immune cell populations in the aged host. With successful completion of the studies proposed
herein through this collaborative partnership, we will provide an unprecedented portrait of the aged ovarian
tumor microenvironment (both tumor- and host-derived) to identify critical determinants of metastatic success
for future mechanistic evaluation and therapeutic intervention.

## Key facts

- **NIH application ID:** 9962320
- **Project number:** 5U01CA236979-02
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Mary Sharon Stack
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $115,875
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962320

## Citation

> US National Institutes of Health, RePORTER application 9962320, Aging and the Ovarian Tumor Microenvironment (5U01CA236979-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9962320. Licensed CC0.

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