# Adrenergic signaling inhibition to enhance the immunogenicity of the ovarian tumor microenvironment prior to PD-1 checkpoint therapy

> **NIH NIH R21** · PONCE SCHOOL OF MEDICINE · 2020 · $438,076

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Armaiz-Pena, Guillermo N.
 PROJECT SUMMARY
Growing evidence suggests that altered psychological states, such as chronic stress, anxiety, and depression
negatively impact patients with ovarian cancer. Multiple studies report that ovarian cancer patients suffer from
increased psychological distress following their diagnosis and during treatment, which contributes to worsened
quality of life and decreased overall survival. These altered psychological states have been linked to increased
stress hormones levels, tumor-associated inflammation, and disease progression. Data supporting this proposal
demonstrates how daily restraint stress leads to increased cytokine levels, macrophage infiltration and activity,
and ovarian cancer progression in animal models. On the other hand, how adrenergic signaling affects anti-
tumor immune responses remains poorly understood. This proposal demonstrates that ascites from ovarian
cancer patients are highly immunosuppressed and T-cells isolated from ascites express an abundance of
inhibitory markers; making this research extremely relevant as recent clinical trials targeting T cells in ovarian
cancer have not been successful. Hence, the overall hypothesis states that stress hormones suppress anti-tumor
T cell responses; thus, blockade by pharmacologic methods will enhance T cell function and improve the efficacy
of checkpoint inhibition therapy in ovarian cancer. Specific Aim 1 will characterize the immunologic changes
that adrenergic signaling has on cytokines and T cell responses in ovarian cancer patients. In Specific Aim 2,
the study team will determine the impact of daily restraint stress on T cell function through pre-clinical models of
ovarian cancer treated with anti-PD-1 therapy and propranolol. The study team is confident that this proposal will
provide a comprehensive approach to dissect the role of chronic stress on cancer-associated immune processes,
such as T cell function and checkpoint inhibition efficacy, that lead to disease progression. Results from this
proposal will identify immune signatures of response and provide a rationale for interventions aimed at preventing
and treating chronic stress experienced by ovarian cancer patients, with the ultimate goal of improving clinical
responses to checkpoint blockade therapy.
OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page

## Key facts

- **NIH application ID:** 10056699
- **Project number:** 1R21CA253555-01
- **Recipient organization:** PONCE SCHOOL OF MEDICINE
- **Principal Investigator:** Guillermo N Armaiz-Pena
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $438,076
- **Award type:** 1
- **Project period:** 2020-09-03 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056699

## Citation

> US National Institutes of Health, RePORTER application 10056699, Adrenergic signaling inhibition to enhance the immunogenicity of the ovarian tumor microenvironment prior to PD-1 checkpoint therapy (1R21CA253555-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10056699. Licensed CC0.

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