# Investigating immune-microbiota interaction in lung cancer

> **NIH NIH R00** · UNIVERSITY OF PENNSYLVANIA · 2021 · $249,000

## Abstract

Project Summary/Abstract
Commensal microbiota inhabits multiple human body sites, primarily in the intestine, and also along the
respiratory tract including the lung. Intestinal microbiota has emerged as an important regulator of
tumorigenesis and therapeutic response in several cancers, yet its role in lung cancer has not been clearly
understood. Changes in the lung microbiota have been associated with several pulmonary disorders; bacterial
infections are highly common in lung cancer patients and closely related to clinical outcomes, but the
underlying biology has been elusive. Therefore, the proposed study aims to investigate the role of local (lung)
and distal (intestinal) microbiota in lung cancer development by using a genetically-engineered mouse model
that recapitulates the activating point mutation of Kras and loss of p53 in human lung adenocarcinoma. Our
preliminary results showed that tumor growth was associated with increased bacterial burden and altered
microbiota composition in the lung, while systemic depletion of microbiota significantly reduced inflammation
and tumor burden, suggesting that the development of a disordered microbiota may induce a dysregulated
immune response to promote lung cancer progression. Here we propose to further interrogate the complex
interactions among commensal microbiota, the host immune system and developing tumor cells to elucidate
the cellular and molecular mechanism(s) by which microbiota promotes tumor initiation and progression.
Specifically, we will (1) establish the role of microbiota-induced γδ T cells in lung tumorigenesis, (2) determine
the effector mechanism(s) of γδ T cells in mediating microbiota-driven tumor promotion, (3) identify the tumor-
promoting bacteria in the lung or intestinal microbiota. While the current research aims to reveal the role of
commensal microbiota in lung cancer by shaping the tumor associated immune response, continued efforts in
the independent phase of this award will be focused on identifying the bacterial species and responding host
pathways involved in tumor promotion which may be targeted for therapeutic intervention in lung cancer.
My career goal is to independently direct an academic research laboratory addressing questions pertaining to
the biology and mechanism of immune-microbiota interaction in cancer. While I have extensive experience in
studying immunology and microbiota, and the use of genetic mouse models, the K99 phase of this project will
allow me to receive further training in advanced bioinformatics and microbiology skills, and to develop novel
gene-editing tools in vivo using autochthonous mouse models of lung cancer. Moreover, I will take advantage
of the superb training opportunities and resources available at the MIT/Broad Institute and further establish
collaborations and networks with the strong, multidisciplinary research communities in the Boston area. These
proposed training and research activities will greatly promote my career devel...

## Key facts

- **NIH application ID:** 10203872
- **Project number:** 5R00CA226400-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Chengcheng Jin
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10203872

## Citation

> US National Institutes of Health, RePORTER application 10203872, Investigating immune-microbiota interaction in lung cancer (5R00CA226400-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10203872. Licensed CC0.

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