# Membrane Ubiquitin Ligase-Driven Immune Evasion in HPV+ Head and Neck Cancer

> **NIH NIH F31** · HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES · 2024 · $46,848

## Abstract

PROJECT SUMMARY
Human papillomavirus (HPV) is the causative agent of 5% of all human cancers, including 25% of head and neck
squamous cell carcinomas (HNSCCs). HPV-driven disease progression requires both persistent infection and
evasion of the host immune response. One mechanism of immune evasion employed by many cancers, including
HPV+ HNSCCs, is the downregulation of major histocompatibility complex class I (MHC-I) on the surface of
tumor cells. MHC-I antigen presentation is crucial for recognition of tumor cells by CD8+ T cells during the
antitumor response and is a major contributor to lack of patient response to immune checkpoint inhibitor therapy.
Our lab has previously shown that an E3 ubiquitin ligase upregulated in HPV+ HNSCCs, MARCHF8,
ubiquitinates immune surface receptors, including MHC-I, for subsequent degradation. Further, a genome wide
CRISPR screen identified genes involved in autophagy, a cellular degradation pathway, as candidates for
negative regulators of MHC-I. Based on these findings, I hypothesize that MARCHF8 upregulation by
papillomaviruses promotes immune evasion by directing MHC-I for autophagic degradation. To test this
hypothesis, I will 1) investigate the mechanism of MARCHF8-mediated MHC-I ubiquitination and degradation via
the autophagy pathway and 2) evaluate inhibition of autophagy as a novel treatment for HPV+ HNSCC. With
these aims, this project will uncover a mechanism of immune evasion during papillomavirus-induced
carcinogenesis.

## Key facts

- **NIH application ID:** 10995141
- **Project number:** 1F31DE034281-01
- **Recipient organization:** HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Lexi Vu
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $46,848
- **Award type:** 1
- **Project period:** 2024-08-16 → 2026-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995141

## Citation

> US National Institutes of Health, RePORTER application 10995141, Membrane Ubiquitin Ligase-Driven Immune Evasion in HPV+ Head and Neck Cancer (1F31DE034281-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10995141. Licensed CC0.

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