Abstract IA17: Cellular interactions and regulatory mechanisms in head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) arises through exposure to environment carcinogens or malignant transformation by human papilloma virus (HPV). Two studies will be discussed. First, we have performed transcriptional profiling of single cells from peripheral and intratumoral immune populations in HPV- and HPV+ HNSCC and healthy donors. We found a spectrum of transcriptional relationships from very similar to highly divergent between the tumor microenvironments (TME) in HPV- and HPV+ HNSCC. Our comprehensive survey of the TME in in HPV- and HPV+ HNSCC highlights the diversity of immune states and complexity of crosstalk between immune populations, and is a benchmark for analysis of the TME in human cancer. Second, many cancer patients do not develop a durable response to current standard of care immunotherapies despite substantial advances in targeting immune inhibitory receptors. A potentially important and unappreciated compounding issue, which may serve as a dominant resistance mechanism, is the inherent systemic immune dysfunction that is often associated with advanced cancer. Although this has been described for decades, primary mechanisms and drivers remain unknown. Lack of response to inhibitory receptor blockade therapy and increased disease burden has been associated with circulating, peripheral CD8+ T-cell exhaustion, which is defined by poor T-cell function linked to increased inhibitory receptor expression (PD1 or LAG3). Our recent studies have assessed if LAG3 and PD1 impact systemic T-cell function.

Citation Format: Dario A.A. Vignali. Cellular interactions and regulatory mechanisms in head and neck cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr IA17.