Abstract 5494: Spatial organization between claudin and the tumor microenvironment in head and neck squamous cell carcinomas
Authors: Maclean Kirsteen , Chandramohan Lakshmi , Rohafza Maryam , Nunns Harry , Parnell Erinn , Au Qingyan , Juncker-Jensen Anna 
Published: March 2024

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading form of cancer worldwide and one of the most difficult and challenging malignancies, with a high level of heterogeneity and a wide range of treatment responses. Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer and accounts for over 90% of cancers that develop within the mucosal epithelium of the oral cavity. Additional carcinogenic risk factors, including tobacco, alcohol and HPV infection are also associated with the pathogenesis of oral carcinogenesis. Unfortunately, today the failure of standard treatment modalities, such as surgery, radiotherapy, and chemotherapy underscore the need to identify better biomarkers of this disease. Advances, especially in spatial technology have created unprecedented opportunities to identify cell types and biomarkers of disease processes, revealing important relationships within the tumor microenvironment (TME) that allow a detailed characterization of specific cell phenotypes defined by co- or lack of expression of multiple markers that may help in predicting clinical responses and mechanisms of resistance to therapy. Recent findings indicate that abnormal expression of claudins (CLDNs) is closely related to the occurrence, progression and prognosis of many solid tumors. Specifically, CLDN6 is expressed in numerous tumors but rarely found in adult normal tissues making it a potential therapeutic target in head and neck tumor types. To investigate this further, expression of CLDN6 and the its relationship with changes within the TME of cohort OSCC tumors was determined using a proprietary comprehensive spatial workflow and gene expression analysis.

Methods: A retrospective analysis was performed on biopsied Formalin-Fixed Paraffin-Embedded (FFPE) samples from OSCC patients with and without a history of smoking and treated +/- chemotherapy. Patient samples representing matched normal tissue to serve as controls were compared to samples derived from OSCC tumors. In order to perform a comprehensive expression profiling of the TME from OSCC tumors we used the spatial MultiOmyx™ immunofluorescence (IF) multiplexing assay with transcriptomic information from bulk mRNA gene expression acquired using the NanoString nCounter® PanCancer IO 360™ panel that includes the Tumor Inflammation Signature (TIS), as well as targets that characterize immune hot, desert, and cold regions in the stroma and tumor epithelium.

Results: We characterized the expression of CLDN6 across the different cohorts of OSCC samples and further investigated the relationship within the tumor immune microenvironment coupled to genes related to the prognosis of OSCC. A better understanding of the TME and gene expression profiling of OSCC tumors and the effect of smoking will allow us to tailor the treatment of patients to continue to improve outcomes.

Citation Format: Kirsteen Maclean, Lakshmi Chandramohan, Maryam Rohafza, Harry Nunns, Erinn Parnell, Qingyan Au, Anna Juncker-Jensen. Spatial organization between claudin and the tumor microenvironment in head and neck squamous cell carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5494.