# Project 1: Targeting the Neutrophil Lineage To Enhance Immune Checkpoint Inhibitor Efficacy in NSCLC

> **NIH NIH P50** · FRED HUTCHINSON CANCER CENTER · 2021 · $82,973

## Abstract

Project Summary/Abstract – Project 1
Although immune checkpoint inhibitor (ICI) therapy has been a tremendous clinical success, just ~20% of non-
small cell lung cancer (NSCLC) patients respond to anti-PD1/PDL1 therapy. In efforts to improve upon this
figure, the field has launched over 800 clinical trials (across all cancer types) testing novel therapeutics in
conjunction with immune checkpoint blockade. Effectively none of these trials adequately address the
neutrophil lineage as a substantial contributor to ICI treatment failure. We provide preliminary data that
neutrophils are the most prevalent immune cell type in NSCLC, inversely correlate with CD8 cellular content,
and preclude the presence of the IFNγ signature, previously shown to correlate with favorable ICI treatment
response. We will perform multiplex-immunohistochemistry on a dataset of FFPE slides obtained from patients
treated with anti-PD1/PDL1 therapy to show that neutrophils associate with poor outcomes. We utilize a novel
mouse model in which the tumor harbors hundreds of mutations to identify the mechanistic determinants of ICI
treatment response and test a novel CXCR1/CXCR2 antagonist to synergize with anti-PDL1 treatment. Lastly,
we will perform a Phase 2 clinical trial testing the combination of the novel CXCR1/CXCR2 antagonist (SX-682,
Syntrix Biosystems, Inc.) and nivolumab in advanced stage NSCLC patients who have previously failed anti-
PD1/PDL1 therapy.

## Key facts

- **NIH application ID:** 10601294
- **Project number:** 6P50CA228944-04
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** A McGarry Houghton
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $82,973
- **Award type:** 6
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10601294

## Citation

> US National Institutes of Health, RePORTER application 10601294, Project 1: Targeting the Neutrophil Lineage To Enhance Immune Checkpoint Inhibitor Efficacy in NSCLC (6P50CA228944-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10601294. Licensed CC0.

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