# Oral immune plasticity, HIV-infected T cell extracellular vesicles, and oral cancer

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $381,781

## Abstract

ABASTRACT
HIV-infected individuals under combination antiretroviral therapy (cART) have approximately 2- to 6-fold
increased incidence rates of oral cancer relative to the general population. These trends in the cART era are
implicitly attributed to persistent and residual HIV replication that induces oral inflammation for tumor
progression. The success of new approaches to control tumorigenesis in the population is contingent to
identifying HIV-specific mechanisms that facilitate tumor development and progression. HIV-infected T cells
produce a variety of immunologically active extracellular vesicles (EVs) to influence intercellular
communication and regulate immune response at both local and distant sites, thus contribute to oral immune
system plasticity. Our preliminary studies explicitly suggest involvement of EVs from HIV-1-infected T cells in
oral cancer progression: 1) HIV-1-infected and control T cells secreted tetraspanin- and acetylcholinesterase-
positive EVs, indicating presence of exosomes in the EV preparation; 2) HIV-infected T cell EVs, but not
control ones, significantly stimulated oral cancer cell proliferation and migration in vitro and tumor growth in
vivo; 3) HIV-infected T cell EVs stimulated ERK phosphorylation without epidermal growth factor receptor
phosphorylation; 4) cART inhibited EV release; 5) EV proteins and miRNA were differentially expressed in
latently HIV-1-infected T cells and control T cells. Taken together, these data are consistent with our
hypothesis that HIV-infected T cell EVs can promote oral cancer development and progression in HIV-infected
individuals under cART and that HIV+ EVs may serve as a target for novel therapeutic approaches to control
oral tumorigenesis in the population. We will test the hypothesis with specific aims to 1) delineate the
mechanism by which HIV-1-infected T cell EVs stimulate oral cancer cell growth and progression. We will
identify signaling pathways of cancer cells that respond to HIV-infected and non-HIV T cell EVs for cell
proliferation, migration, and invasion; 2) identify functional EV production and cargo content in latently HIV-
infected T cell EVs in response to cART. We will investigate how cART affects EV release and conduct
proteomics, miRNomics, and lipidomics to access EV molecular signatures that differentiate HIV-infected from
non-HIV T cells. This proposed research will expand knowledge on oral immune system plasticity mechanisms
for developing preventive and therapeutic approaches.

## Key facts

- **NIH application ID:** 9851749
- **Project number:** 5R01DE026925-04
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Ge Jin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,781
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851749

## Citation

> US National Institutes of Health, RePORTER application 9851749, Oral immune plasticity, HIV-infected T cell extracellular vesicles, and oral cancer (5R01DE026925-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851749. Licensed CC0.

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