PloS one
Spatial organization of HPV-associated immune programs across tissue compartments in oropharyngeal cancer
By Wakisaka N, Moriyama-Kita M, Kondo S and 4 others.
Abstract
Background
Human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) is characterized by a distinct immune microenvironment; however, the biological significance of immune-related transcriptional programs may vary according to their spatial localization. We investigated the spatial organization of HPV-associated transcriptional programs across anatomically distinct tissue compartments in OPC.
Methods
An oropharynx-restricted The Cancer Genome Atlas (TCGA)-oropharyngeal squamous cell carcinoma (OPSCC) cohort comprising 77 tumors (51 HPV-positive and 26 HPV-negative) was analyzed using single-sample gene set enrichment analysis (ssGSEA). Spatial transcriptomic profiling using GeoMx Digital Spatial Profiling was evaluated in lymphoid follicular regions (LFRs) and tumor tissue regions (TTRs) from six OPC patients (four HPV-positive and two HPV-negative), with the patient treated as the primary experimental unit. Tumor-free surrounding palatine tonsillar tissue (PTT) was analyzed in an independent microarray cohort comprising 23 HPV-positive and four HPV-negative cases. Eight prespecified immune- and metabolism-related transcriptional programs were evaluated, with additional exploratory cell-type deconvolution and overall survival analyses.