# DNA-based Immune Phenotyping in HNSCC for Biomarkers of Response to Immunotherapy

> **NIH NIH R01** · BROWN UNIVERSITY · 2024 · $631,543

## Abstract

PROJECT SUMMARY/ABSTRACT
Head and Neck Squamous Cell Carcinomas (HNSCCs) are devastating upper airway tumors that are associated
with an immunosuppressive network impacting the tumor microenvironment, bone marrow and the peripheral
blood compartments. The development of novel biomarkers of cancer immunity have not kept pace with
breakthroughs in our understanding of cancer-associated inflammation and its relationship with abnormal
hematopoiesis and the production of immunosuppressive leukocyte populations. Nor have biomarkers kept pace
with clinical indications for use of immunomodulatory therapies. Here, we address the gap in clinically applicable
immune biomarkers by first developing unique immuno-methylomic tools to identify aberrant peripheral immune
cell populations, followed by the application of such tools for studying HNSCC survivorship. The FDA recently
approved pembrolizumab with or without chemotherapy as a first-line treatment for metastatic, or unresectable
recurrent disease, which is poised to dramatically increase the number of patients receiving immunotherapy for
HNSCC, further underscoring the critical need to identify biomarkers of response to treatment, even before de
facto issues of drug cost. Further, recent successful trials of immunomodulatory agents treating late stage
HNSCC reveal that there is a crucial role for the immune system in disease survival and prognosis. To
understand and quantify immune status, we propose to apply novel DNA methylation-based immune
phenotyping biomarkers that will define the immune suppressive state and allow us to intensively study its
relationship to immunotherapy treatment response in HNSCC. The proposed study will draw from two
independent, comparable, prospectively collected patient cohorts at NCI-designated Comprehensive Cancer
Centers. Results from single cell tracing approaches to follow clones of cells in-vivo in cancer patients showed
dramatic evidence that the intrinsic ability to attract new immune cells to the tumor results in improved checkpoint
blockade activity. This finding strongly supports our approach to identifying biomarkers of checkpoint blockade
response through measures in the peripheral blood. As new immunotherapies are developed for HNSCC, it is
crucial to mediate the effects of the host’s compromised immune system. The new generation of epigenetic
techniques for immune profiling will provide biomarkers that are useful both in assessing immune status and in
addressing mechanisms of immune modifiers.

## Key facts

- **NIH application ID:** 10757635
- **Project number:** 5R01CA253976-04
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Brock C Christensen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $631,543
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757635

## Citation

> US National Institutes of Health, RePORTER application 10757635, DNA-based Immune Phenotyping in HNSCC for Biomarkers of Response to Immunotherapy (5R01CA253976-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10757635. Licensed CC0.

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