# Targeting the innate immune response in HNSCC

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $468,267

## Abstract

Abstract
The immune system is a complex but highly plastic biological defense system that normally protects the host
against infection and damage. However, in some disease states, such as cancer, the usually well-orchestrated
immune response fails to protect the host and instead exacerbates disease. Because the immune system is
highly plastic, however, novel therapeutics may be able to restore normal immune responses that combat
cancer. There is a critical need to develop novel therapies for oral cancers, such as head and neck squamous
cell carcinoma (HNSCC), a deadly and disfiguring disease that accounts for an estimated 59,340 cases
(43,390 men and 15,950 women) and 12,290 deaths each year in the United States. The incidence of HNSCC
is rapidly rising in the United States and worldwide, in part due to increases in human papillomavirus (HPV)
associated oropharynx cancers. While current immune therapies hold new promise for the treatment of cancer,
the checkpoint inhibitor nivolumab (anti-PD-1) recently demonstrated only modest single agent activity in
recurrent/metastatic HNSCC, as one-year survival and response rates were only 36% and 13%, respectively,
in a Phase 3 trial. Improved therapeutic approaches that target additional mechanisms of immune escape in
combination with checkpoint inhibitors could hold promise for this disease. Our recent studies (Nature 2016)
showed that immune suppressive Tumor Associated Macrophages (TAMs) promote HNSCC immune escape.
We found that two macrophage proteins, phosphatidylinositol-4,5-bisphosphate 3-kinase gamma PI3Kγ
inhibition repolarized macrophages and synergized with anti-PD-1 to enhance recruitment and activation of
IFNγ+ cytotoxic CD8+ T cells. These results indicate that therapeutic strategies that target TAMs as well as T
cell checkpoints could improve HNSCC patient outcomes. We propose to test the overall hypothesis that
therapeutic strategies that block macrophage-mediated immune suppression will synergize with T cell targeted
therapeutics to improve outcomes in HNSCC disease. The specific aims of this proposal are: 1) To determine
how immune suppressive myeloid cells are recruited to HNSCC tumors. 2) To identify how myeloid cell
polarization is controlled during HNSCC tumor progression. 3) To identify novel immune therapeutic strategies
and immune biomarkers for HNSCC disease.

## Key facts

- **NIH application ID:** 9980195
- **Project number:** 5R01DE027325-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Judith A VARNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $468,267
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980195

## Citation

> US National Institutes of Health, RePORTER application 9980195, Targeting the innate immune response in HNSCC (5R01DE027325-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9980195. Licensed CC0.

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