Sponsor: Investigator-initiated
Project Period:
Current Status: Recruiting
Overview
The long-term goal of this study is to better understand innate and adaptive immune responses to head and neck cancers (HNC) for the development of effective immunotherapeutic approaches to combat the disease. We have reported that pre-cancerous lesions and other cancer cells at the invasive front of oral cancer overexpress human beta-defensin-3 (hBD-s), a secreted innate immune peptide. Human papillomavirus (HPV) associated HNCs also express hBD-3. The expression of hBD-3 is induced by activation of epidermal growth factor receptor (EGFR), WNT signaling, and by inactivation of the tumor suppressor p53 - all three pathways are implicated in HNC development. Data indicates that tumoral expression of hBD-3 is not an immune response during tumorigenesis and that hBD-3 can be developed as a potential biomarker of HNC. Expression of hBD-3 is associated with accumulation of macrophages and myeloid-derived suppressor cells (MDSCs) and production of tumor-promoting molecules, potentially forming a positive feedback loop, driving tumor progression.
The Jin Laboratory and collaborating clinicians from University Hospitals are investigating the mechanism by which hBD-3 promotes HNC progression through recruitment and activation of tumor-promoting myeloid cells and clinical outcomes in patients in association with hBD-3 expression, tumoral and circulating immune cells, and expression of check point molecules. The study involves collection of demographic and clinical data, blood and lesion samples for immunological analysis and hBD-3 expression, and animal models to explore novel immunotherapy approaches. The study is additionally investigating influence of HIV on oral HPV infection and progression to HNC.
Project Team
Tracey Bonfield, PhD - Co-Investigator
Lechuang Chen, PhD - Postdoctoral Fellow
Kate Clancy, BA - Student Research Assistant
Santosh Ghosh, PhD - Research Associate
Michael Gibson, MD - Co-Investigator
Ashlee Jeter, BS - Research Assistant
Ge Jin, PhD - Principal Investigator
Tom McCormick, PhD - Co-Investigator
Bridget Patrick, MS, CCRC - Study Coordinator
Bingcheng Wang, PhD - Co-Investigator
Aaron Weinberg, DMD, PhD - Co-Investigator
Hong Yue, MD, PhD - Research Associate
Chad Zender, MD - Co-Investigator