The Oral Periodontal Pathogens and Checkpoint Blockade in NSCLC
Abstract
Lung cancer causes more death than colorectal, breast, and prostate cancers combined. Therapies targeting T cell inhibitory checkpoint pathways can provide durable responses to common cancer including lung cancer at unprecedented rates. Yet only a minority of patients respond to these treatments. New evidence suggests that gut bacteria affect immunotherapy response. Our oral cavity harbors the second number of bacteria after our gut. Studying requires studying whether oral bacteria behave like gut bacteria to influence immunotherapy response in lung cancer patients. Based on LSL-Kras mouse lung cancer model we have found that some oral bacteria that drive periodontitis greatly promote lung cancer development while some oral bacteria associated with healthy gum didn’t influence lung cancer development. P gingivalis, one of the major oral bacteria found in periodontitis patients not only promoted lung tumor development but also reduced the power of checkpoint inhibitors on lung cancer treatment. Thus, our work has revealed functional interconnections between oral bacteria, spontaneous lung tumor development, and anti-tumor reaction to checkpoint inhibitors. In this proposed project, we will work to address the following questions: What are the mechanisms that underline the link between the oral pathogen bacteria and lung tumor resistance to checkpoint inhibitors therapy? Can we determine oral bacteria that affect the resistance of lung cancer to neoadjuvant checkpoint inhibitors in NSCLC patients? Can we modify oral bacteria to sensitize them to checkpoint inhibitor treatment? We think that oral periodontal pathogens such as P gingivalis can modulate lung cancer development and/or the therapeutic response of lung tumor to checkpoint inhibitor therapy. This project will emphasize one of the important LCRP Areas, Understanding mechanisms of resistance to treatment (primary and secondary). Suppose we can find specific oral bacteria commonly seen in periodontitis linked to lung cancer development and/or the outcomes of immunotherapy; in that case, we should have better ways to target those bacteria and will have immediate implications in immunotherapy for lung cancer patients. This project is also useful for scientists to learn fundamentally important information about how oral bacteria function is related to lung cancer development. This project will help early-stage lung cancer patients receive checkpoint inhibitors new adjuvant therapy and may extend to all lung cancer patients, in particular Veteran patients, to develop and maintain good oral care habits, and eventually increase the survival rate in patients with lung cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310667
Entities
People
- Qingsheng Li
Organizations
- New York University
- United States Army