# Strategies to Overcome Immune Resistance in Head and Neck Cancers

> **NIH NIH P01** · YALE UNIVERSITY · 2023 · $1,411,624

## Abstract

SUMMARY - OVERALL PROGRAM
Head and neck squamous cell carcinoma (HNSCC) is a worldwide public health problem and cancer patients
have limited effective treatment options. For the first time in 50 years, overall survival has been impacted in
HNSCC patients with the FDA approval of anti-PD1 monotherapy. However, only a small subset of HNSCC
patients derives clinical benefit. The goal of our Program is to build upon the incremental successes of
immunotherapy and improve clinical outcomes by addressing the two main barriers to achieving clinical
response to immunotherapy: (a) the tumor's overall poor antigenicity (intrinsic mechanism), which limits the
generation of antitumor immunity, and (b) innate and adaptive immune suppression (extrinsic mechanism) that
results in immune tolerance. The overarching goal of this Program Project (P01) is to gain further insight
into both mechanisms of HNSCC immune resistance, so as to overcome them through the rational
design and rapid translation of novel combinatorial immunotherapeutic strategies which will eventually
increase the number of HNSCC patients who may derive clinical benefit from immunotherapy. To
accomplish these goals, the Program seeks to achieve the following overall aims:
Overall Aim 1: Uncover both intrinsic and extrinsic mechanisms of immune resistance in HNSCC
patients.
Overall Aim 2: Develop rationale, novel combinatorial strategies that translate into clinically
meaningful responses.
These aims leverage innovations in concepts and methodology and are coupled with expertise in head and
neck oncology, HLA biology, antigenic peptide discovery, lymphocyte and myeloid cell biology,
genomics/epigenomics, antibody drug conjugate therapy, and mouse modeling. The broad aims will be
implemented with 3 inter-related and focused Projects and 3 Shared Resource Cores:
- Project 1: Therapeutically improving HNSCC antigenicity through epigenetic reprogramming (Dr. Pai)
- Project 2: Redirecting pre-existing anti-viral immunity to HNSCCs with APECs (Dr. Cobbold)
- Project 3: Myeloid-lymphoid cell crosstalk in HNSCC therapy (Dr. Pittet)
- Administrative Core (Drs. Pai/Wirth)
- Core 1: Diagnostic Immunopathology and Imaging Core (Drs. Sadow/Faquin)
- Core 2: Immune Bioinformatics and Computational Biology Core (Drs. Xavier/Sartor)
 At the end of the 5 years, we aim to have initiated several clinical trials of combinatorial strategies in
head and neck cancer patients, which will be grounded on the data generated from this P01. We expect the
overall Program will have a significant impact on the clinical outcomes of head and neck cancer patients and
its discoveries also have the potential to impact the larger immuno-oncology field.

## Key facts

- **NIH application ID:** 10690599
- **Project number:** 7P01CA240239-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Sara Isabel Pai
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,411,624
- **Award type:** 7
- **Project period:** 2019-09-19 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10690599

## Citation

> US National Institutes of Health, RePORTER application 10690599, Strategies to Overcome Immune Resistance in Head and Neck Cancers (7P01CA240239-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10690599. Licensed CC0.

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