Institution: Hebrew University of Jerusalem
Grant Type: Project Grant
Award Year: 2025–2028
Research Topics: Oral Cancer
Prof. Avi-Hai Hovav earned a PhD in Immunology and Microbiology from the Hebrew University in 2005, followed by postdoctoral training at Harvard University. In 2008, he returned to Hebrew University as a Lecturer, advancing to Senior Lecturer in 2011, Associate Professor in 2014, and Full Professor in 2019. Dr. Hovav’s research centers on the development and function of the oral mucosal immune system, with a focus on the oral epithelium and its key sentinel cells, Langerhans cells. His laboratory employs murine models to investigate the mechanisms driving oral cancer development, aiming to translate these findings to human disease for therapeutic insights.
About the Research
Oral Squamous Cell Carcinoma (OSCC) is the most common oral cancer and a leading cause of cancer-related death. Tumors with higher nerve density are often more aggressive and linked to increased metastasis, pain, and poorer survival. However, the factors driving nerve growth in tumors remain unclear. Our research focuses on immune cells in the oral lining that regulate nerve growth, particularly Langerhans cells (LCs) and macrophages. Our preliminary studies revealed that LCs maintain healthy nerve density by releasing IL-1β, which stimulates Nerve Growth Factor (NGF) production in epithelial cells. However, in OSCC, LCs are depleted and replaced by macrophages, which produce higher levels of NGF, leading to excessive nerve growth that may fuel tumor progression.
We hypothesize that early in OSCC, LCs regulate nerve growth to support immune defense. As OSCC advances, LCs are replaced by macrophages, driving excessive nerve growth and promoting cancer progression. To test this, we will: (1) study how nerve density impacts early OSCC growth; (2) explore how macrophages drive nerve growth and tumor aggressiveness; (3) assess how increased nerve density shapes the tumor environment; and (4) validate our findings in human OSCC tissues. Our innovative approach highlights a previously unrecognized role for immune cells in controlling nerve growth in OSCC. This work could lead to new treatments that limit nerve-driven cancer progression, improving outcomes for OSCC patients.
