# Dissecting temporal and spatial dynamics of immunotherapy resistance

> **NIH NIH K23** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2021 · $173,772

## Abstract

PROJECT SUMMARY
Immune checkpoint inhibitors (ICI) are now used as first line therapy in patients with recurrent or metastatic
head and neck squamous cell carcinoma (HNSCC), yet, only one out of six patients respond. How the
composition and spatial organization of the tumor immune microenvironment relates to ICI efficacy in HNSCC
is currently poorly understood. What is known, is that cancers are dynamic, evolving temporally and spatially in
response to therapeutic pressures, with building support suggesting that on treatment assessment is more
predictive of ICI response than assessment of pre-treatment tissue. In this proposal we will apply innovative
single cell sequencing and imaging approaches to answer a critical question impeding progress in head and
neck cancer care: how the spatial and temporal evolution of tumor and immune cells impacts ICI resistance.
Aim 1 will distinguish tumor cell programs that associate with ICI resistance in primary tissue and serially
measure alterations in these genes in circulating tumor cells. Aim 2 will define how T and B cell subpopulations
and spatial architecture change with ICI initiation and how alterations relate to ICI resistance. Completion of
these mentored aims will set the stage for the long term goal of developing improved predictive biomarkers of
ICI response and identifying new targets for combinatorial therapies. This career development proposal
presents a five-year plan to both accomplish the outlined scientific aims as well as a detailed training program
to ensure the candidate’s transition to research independence. The candidate is an Instructor in
Otolaryngology-Head and Neck Surgery at Harvard Medical School, Massachusetts Eye and Ear and
Massachusetts General Hospital. The training aims, which include hand on experience, coursework and
seminars focused on immunogenomics, build on the candidate’s previous research experience in cancer
genomics and clinical experience as a head and neck cancer surgeon. Mentorship will be provided by thought
leaders in single cell imaging and sequencing, bioinformatics, biomarker science, and cancer immunology
including the primary mentorship team of Dr. Shannon Stott, PhD, Keith Flaherty, MD and Nir Hacohen, PhD
at Massachusetts General Hospital Cancer Center.

## Key facts

- **NIH application ID:** 10215652
- **Project number:** 1K23DE029811-01A1
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Daniel Faden
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $173,772
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215652

## Citation

> US National Institutes of Health, RePORTER application 10215652, Dissecting temporal and spatial dynamics of immunotherapy resistance (1K23DE029811-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10215652. Licensed CC0.

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