Author(s)
Christopher A. Maroun, MD
Gangcai Zhu, MD PhD
Margueritta El Asmar, MD
Christine G. Gourin, MD MPH
Peter S. Vosler, MD PhD
Rajarsi Mandal, MD
Affiliation(s)
Johns Hopkins University School of Medicine;
Abstract:
Educational Objective: At the conclusion of this presentation, participants should be able to compare differences in immune infiltration and expression of immunomodulatory markers in HPV negative head and neck squamous cell carcinoma within different anatomical subsites. Objectives: To investigate differences in immune infiltration, immunomodulatory marker expression, and associated survival in HPV negative HNSCC within different anatomical subsites, which has not been investigated in this cohort. Study Design: Retrospective analysis. Methods: Normalized mRNA expression data were downloaded from the Cancer Genome Atlas (TCGA) database. Deconvoluted immune cell population data using the CIBERSORT algorithm were retrieved from Thorsson et al (2018). Cell fractions and marker expression were compared between subsites using the Kruskal-Wallis test. Patients were categorized into high and low fraction groups using the 30th percentile for each subsite. Groups were used to calculate overall (OS) and progression free (PFS) survival for laryngeal and oral cavity tumors separately. Adjustment for multiple comparisons was performed using the Benjamini-Hochberg method, with false discovery rate of 0.05. Results: 382 HPV negative HNSCC patients were included; 247 (64.7%) oral cavity, 106 (27.7%) larynx, 23 (6.0%) oropharynx, and 6 (1.6%) hypopharynx. There were significantly different fractions of naïve B cells (p<0.0001), plasma cells (p<0.0001), lymphocytes (p<0.0001) and macrophages (p<0.001) between subsites. Subsites showed differential expression of immunomodulatory markers PVRIG (p=0.0033), ICOSLG (p<0.0001), and GITR (p<0.0001). A low lymphocyte/macrophage ratio resulted in significantly worse OS (HR=2.39, p=0.0025) and PFS (HR=2.13, p=0.0155) exclusively within laryngeal tumors, but not oral cavity tumors (OS HR=1.25, p=0.253; PFS HR=0.93, p=0.729). Conclusions: Different subsites within the head and neck appear to harbor altered immune tumor microenvironments that are independent from the effects of HPV related oncogenesis. These differences appear to have differential consequences on survival, providing rationale for subsite stratification in the development of future immune based clinical trials.