Linda Marklund

Background: Despite aggressive surgery coupled with radiation/chemoradiation, the 5-year overall survival rate of oral squamous cell carcinoma (OSCC) has stagnated at 50% for decades. While cancer immunotherapy holds promise, OSCC patients typically experience only modest enhancements compared to other cancer types. Advancing immunotherapies requires a deeper understanding of cancer immunity mechanisms. Insights into neutrophil immunity, with their potential to influence pro- and anti-cancer responses, particularly within tumor-draining lymph nodes (TDLNs), remain limited.Goal: To dissect the immunomodulatory roles of neutrophils in TDLNs across various stages of OSCC and characterize their potential as facilitators of metastasis within these nodes. The project has 4 aims that synergistically build upon one another.Methods: Several techniques, including single-cell sequencing, flow cytometry, and spatial transcriptomics, will be deployed to characterize fresh samples of OSCC tumors, TDLNs, and non-TDLNs, alongside lymph nodes from non-cancer patients. Boyden chambers, in conjunction with an orthotopic xenograft model, will be utilized to investigate the involvement of tumor-associated neutrophils in cancer dissemination to TDLNs.Clinical Implications: A successful outcome has the potential to catalyze the development of novel strategies aimed at bolstering immune responses against cancer, thereby potentially enhancing the effectiveness of existing cancer immunotherapies.