# Dissecting Tumor-Immune Interactions in HIV-HPV Co-Infection-Associated Oropharyngeal Cancer using Single Cell Sequencing and Novel Mouse Models

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $578,249

## Abstract

Project Summary/Abstract
Oropharyngeal squamous cell carcinoma (OPSCC) has emerged as a significant global health concern, with
increasing incidence attributed to human papillomavirus (HPV) infection. Additionally, individuals living with
HIV/AIDS (PLWH) face a higher risk of developing OPSCC. Understanding the synergistic relationships between
HIV and oral HPV infection in OPSCC development is critical for advancing prevention, diagnosis, and treatment
strategies. CD8+ T cells play a pivotal role in antiviral immunity and tumor surveillance. However, the impact of
HIV infection on CD8+ T cells remains largely unexplored. Recently, we have identified an HPV integration
hotspot in the PD-L1 gene, contributing to CD8+ T cell exhaustion. In addition, our single-cell analysis revealed
a unique subset of exhausted CD8+ T cells associated with HIV-HPV co-infection in the OPSCC
microenvironment. We hypothesize that HIV co-infection induces elevated dysfunction/exhaustion of tumor-
infiltrating lymphocytes (TILs), particularly CD8+ T cells, in the OPSCC microenvironment. As a multi-PI
application, combining our expertise in single-cell analysis and functional analysis of HIV mouse models and
CD8+ T cells, we will investigate the impact of HIV infection on the immune cell landscape of HPV-positive
OPSCC (Aim 1). Additionally, we will characterize the phenotype and specificity of tumor-infiltrating CD8+ T cell
receptors (TCRs) and correlate them with cellular exhaustion status in the context HIV-HPV co-infection (Aim 2).
Furthermore, we will establish a novel mouse model that faithfully recapitulates HIV-HPV co-infection in OPSCC
to explore dynamic interactions between viral infection, tumor progression, and CD8+ T cells (Aim 3). Additionally,
we will investigate the impact of combined antiretroviral therapy (ART) and immune checkpoint blockade on
restoring tumor-reactive CD8+ T cell function and preventing HPV-induced neoplastic growth. This research
aims to enhance our understanding of HIV-HPV co-infection's influence on immune responses and immune
evasion in oropharyngeal cancer. Findings may inform novel therapeutic strategies to enhance immune
responses and improve clinical outcomes for OPSCC patients living with HIV and have broader implications for
other HPV-associated malignancies.

## Key facts

- **NIH application ID:** 10892706
- **Project number:** 1R01CA291607-01
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** HARRIS GOLDSTEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $578,249
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892706

## Citation

> US National Institutes of Health, RePORTER application 10892706, Dissecting Tumor-Immune Interactions in HIV-HPV Co-Infection-Associated Oropharyngeal Cancer using Single Cell Sequencing and Novel Mouse Models (1R01CA291607-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10892706. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*