# Investigating the neutrophil-sensory neuron crosstalk in lung cancer

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $455,419

## Abstract

Many types of solid tumors are innervated by distinct branches of the nervous system that, like
the immune system, sense and respond to internal and environmental stimuli. However, nerves
have long been viewed as passive bystanders in cancer. It is poorly understood how the nervous
system regulates the tumor-associated immune responses, and what factors in the tissue-specific
microenvironment shape tumor innervation. Therefore, the overarching goal of our research is to
develop an in-depth and broad understanding of neuro-immune interaction in cancer with a focus
on the bi-directional crosstalk between the sensory neurons and the tumor microenvironment
(TME), and to explore whether we can target such interactions for more effective cancer treatment.
Of particular interest, lung-innervating nociceptors are specialized sensory neurons that control
cough and pain, the most common clinical symptoms in lung cancer patients. While nociceptors
were shown to regulate lung immune cells in allergy and bacterial infections, little is known about
their roles in oncogenesis. Our central hypothesis is that nociceptive sensory neurons play a
key role in promoting lung cancer development via cross-talking to the immune cells, particularly
the tumor-associated IL-17+T cells and neutrophils. As such, targeting the nociceptive neural
pathways can improve the cancer response to immunotherapy by reprogramming the tumor
immune microenvironment. Experimentally, we will combine genetically engineered mouse
models that faithfully reproduce the human lung adenocarcinoma with cutting-edge approaches
in cellular immunology, cancer genetics, and functional manipulations of neuronal circuits.
Specifically, we propose to test our central hypothesis by (1) establishing the role of tumor
innervation by sensory neurons in lung cancer, (2) elucidating the mechanisms by which tumor
innervation shapes the cancer-associated immune responses, (3) determining the pre-clinical
efficacy of targeting the nociceptive neural pathway in combination with checkpoint-based
immunotherapy.
Our study will provide fundamental insights to the emerging yet poorly understood functions and
regulatory mechanisms of the sensory nervous system in the TME, especially their role in cancer-
associated immune responses. Furthermore, the conceptual and technological advances
generated here will build the foundation for future investigations into neuro-immune interactions
in additional cancer types, shedding light on sensory neural pathways and neuro-immune
crosstalk that can serve as novel therapeutic targets for cancer prevention and treatment.

## Key facts

- **NIH application ID:** 10798227
- **Project number:** 5R01CA280601-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Chengcheng Jin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $455,419
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798227

## Citation

> US National Institutes of Health, RePORTER application 10798227, Investigating the neutrophil-sensory neuron crosstalk in lung cancer (5R01CA280601-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10798227. Licensed CC0.

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