# Local microbiota signatures of pro-tumor immunity and checkpoint inhibition susceptibility in lung cancer

> **NIH NIH R37** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $695,920

## Abstract

Abstract. Despite the declining prevalence of smoking in the US, lung cancer continues to be the leading cause
of cancer deaths. Treatment of lung cancer with PD-1 blockade has become first line therapy of most non-small
cell lung cancer (NSCLC). However, given the variable effectiveness of immunotherapy in this disease there is
a need to better understand factors that affect individual’s response to this therapy. The lung microbiota plays
an important role in host immune responses affecting subject’s susceptibility to inflammatory airway diseases.
We have demonstrated that lower airway microbiota is associated with Th17 phenotype in the lower airways. In
lung cancer, we identified a dysbiotic signature in the lower airways called pneumotypeSPT that is associated with
transcriptomic signatures associated with lung carcinogenesis. Our preliminary data shows that subjects with
lower airway microbiota characterized as pneumotypeSPT may have increased mortality and increased immune
checkpoint inhibited tone. While gut microbiota signatures are partially associated with PD-1 blockade response,
the effects of the lower airway microbiota on the immune tone and PD-1 blockade susceptibility are not known.
Thus, we hypothesize that lower airway dysbiosis (pneumotypeSPT) alters the host inflammatory
phenotype in the tumor microenvironment affecting the response to PD-1 blockade. To study this, we will
utilize a scientifically rigorous approach to conduct this pathophysiological investigation using prospective
airway, stool, and blood samples collected before and after PD-1 blockade treatment of subjects with advanced
NSCLC. We will evaluate airway/stool microbial signatures associated subjects’ response to PD-1 blockade by
longitudinal assessment of the progression free survival (Aim 1). In addition, we will perform longitudinal
sampling of airways, stool, and blood to expand our mechanistic understanding of the dynamic changes in the
microbiome and host immune response during PD-1 blockade treatment (Aim 2). Validation and extension of
the assessment of the microbiome and host inflammatory profile will be accomplished by using complementary
approaches (microbiota: 16S rRNA gene and metatranscriptome sequencing; inflammation: airway brush
transcriptome, polychromatic flow cytometry, and single cell RNA sequencing of T cells). In Aim 3 we will use a
preclinical mouse model of lung cancer that will allow us to evaluate the effects of dysbiosis on the lower airway
immune tone and PD-1 blockade susceptibility. Identification of microbial signatures that affect the response to
this first line therapy will be key to a personalized therapeutic approach and will identify novel modifiable targets.
Lay summary. The treatment of lung cancer, the leading cause of cancer deaths in the U.S., has been
revolutionized by the use of immunotherapy. However, the response to this therapy is variable and recent data
suggest that microbes that colonize our bodies (called microbio...

## Key facts

- **NIH application ID:** 9865697
- **Project number:** 1R37CA244775-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Leopoldo Nicolas Segal
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $695,920
- **Award type:** 1
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9865697

## Citation

> US National Institutes of Health, RePORTER application 9865697, Local microbiota signatures of pro-tumor immunity and checkpoint inhibition susceptibility in lung cancer (1R37CA244775-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9865697. Licensed CC0.

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