# Role of persistent type I IFN signaling in immune suppression and tumorigenesis during chronic HIV infection

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $312,000

## Abstract

Project Summary
 HIV is a disease of inflammation and chronic immune activation. Ultimately, this results in severe immune
dysfunctions and occurrence of other comorbidities, including cancer. In HIV disease, the mechanisms
underlying chronic inflammation and how they contribute to immune deterioration and increased risk in cancer
diseases as well as whether the ability to therapeutically interfere with this process could restore immune
competence remain unclear. Across multiple species, including mouse models of chronic virus infection, SIV
infection in primates, and HIV infection in humans, mounting evidence implicates type I interferon (IFN-I)
signaling as a central mechanism underlying the chronic inflammation that drives the development of
suppressive immune environment that promote cancer growth. The goal of this proposal is to elucidate the
relationship between chronic IFN-I signaling, inflammation, immune exhaustion, and the development of an
immuno-suppressive tumor niche that favors tumor growth.
 To achieve this goal, we will utilize a humanized mouse model that 1) allows engraftment and growth of
multiple tumor cell lines and 2) recapitulates IFN-I induced immune activation and exhaustion during chronic HIV
infection in vivo. We will utilize novel strategies to promote or block IFN-I signaling in vivo and an innovative
approach to specifically generate tumor specific T cells to: (1) define the precise contribution of IFN-I signaling
during HIV infection to the development of immuno-suppressive tumor enviroment and exhaustion of anti-tumor
T cell that favor cancer growth; and (2) investigate if blocking chronic IFN-I signaling during chronic HIV infection
can improve anti-tumor immunity and efficacy of immune checkpoint inhibitor blockade.
 Once completed, we strongly feel that our studies will significantly advance the understanding of the
fundamental mechanisms that result in immune dysfunction and increased risk of AIDS and non-AIDS-related
cancer. This will also provide the foundation, rationale, and system for future studies to define and therapeutically
target inflammation and immune activation for cancer treatment with HIV infection.

## Key facts

- **NIH application ID:** 9916732
- **Project number:** 5R01CA239261-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** SCOTT G KITCHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $312,000
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9916732

## Citation

> US National Institutes of Health, RePORTER application 9916732, Role of persistent type I IFN signaling in immune suppression and tumorigenesis during chronic HIV infection (5R01CA239261-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9916732. Licensed CC0.

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