Immune-Related Gene Expression Profile at Peritumoral Tonsillar Tissue Is Modified by Oropharyngeal Cancer Nodal Status.

ABSTRACT

Secondary lymphoid organs, such as lymph nodes and tonsils, serve as an interface between the immune system and tumor cells as an initial antigen-presentation site, crucial in antitumor immune response and disease progression. In oropharyngeal cancers originating from palatine tonsils, it was hypothesized that characterizing the immunologic process occurring in the peritumoral tonsil tissue would elucidate immune mechanisms of the lymphatic spread of the disease. A total of 33 patients were enrolled and divided into two cohorts. In Cohort 1 (6 patients), gene expression profiles at the peritumoral lymph regions and tumor regions were analyzed using the whole-transcriptome atlas. In the peritumoral lymph regions, 237 genes were up-regulated in metastasis-negative cases compared with metastasis-positive ones, but only 1 gene was up-regulated in tumor regions. In Cohort 2 (27 patients), microarray analysis of peritumoral tonsil tissue revealed 192 up-regulated genes. Gene ontology analysis revealed the significantly enriched Gene Ontology terms associated with T-cell activation; top 10 hub genes, as ranked by degree, were PTPRC, TLR4, CD80, CD40, STAT3, CD28, CD40LG, CD44, CCR7, and IL7R. Gene set enrichment analysis combined with principal component analysis were used to effectively classify patients as lymph node metastasis positive or negative. These findings suggest peritumoral tonsils as a potential target for investigating the immune mechanisms associated with the lymphatic spread of the disease in oropharyngeal cancers.