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School of Dental Medicine

(Jin) Beta-defensins in Immunological Oncogenesis

(Jin) Beta-defensins in Immunological Oncogenesis

Beta-defensins in Immunological Responses and Immunotherapy in Oncogenesis

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

Principal Investigator

Ge Jin, PhD

ge.jin@case.edu

Funding

NIH/NIDCR