# Mechanisms of Tumor Derived Neutrophil Induced Apoptosis in Lymphocytes

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $218,585

## Abstract

ABSTRACT
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. Unfortunately, such trials have been based largely on
theoretical considerations and not by data obtained from actual human cancer specimens. Notably, very few of
these trials address myeloid lineage cells and none of them address the neutrophil lineage. Our group recently
undertook a comprehensive immune phenotyping project to identify potential immune suppressive factors in
human NSCLC. We found that neutrophils were the most prevalent immune cell type out of the 51 immune cell
types and subtypes assessed. More importantly, the presence of neutrophil lineage cells inversely correlated
with CD8+ lymphocyte content within the TME. Here, we will show that tumor derived neutrophils antagonize
CD8+ lymphocyte function both in vitro and in vivo and determine the mechanisms by which they do so.
Furthermore, we will perform clinical trials in tumor bearing mice to show that neutrophil depleting drugs will
improve the efficacy of immune checkpoint inhibitor therapy.

## Key facts

- **NIH application ID:** 10168478
- **Project number:** 5R01CA221295-04
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** A McGarry Houghton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $218,585
- **Award type:** 5
- **Project period:** 2018-07-17 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168478

## Citation

> US National Institutes of Health, RePORTER application 10168478, Mechanisms of Tumor Derived Neutrophil Induced Apoptosis in Lymphocytes (5R01CA221295-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10168478. Licensed CC0.

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