Abstract
ObjectivesTo investigate the role of interleukin-33 (IL-33) in head and neck squamous cell carcinoma (HNSCC).Materials and MethodsRNA-seq data of 520 cases of HNSCC were retrieved from The Cancer Genome Atlas. The tumor microenvironment was deconstructed by xCell using bulk RNA-seq data. The cohort was dichotomized by the median IL-33 expression level. Immune cell components and molecular markers were compared between the high and low IL-33 groups. The prognostic value of IL-33 was evaluated by the log-rank test. Differential gene expression analysis and KEGG pathway enrichment analysis were also conducted. The relationship between the IL-33 expression level and the abundance of its potential cellular sources was evaluated by Pearson’s partial correlation test. Subgroup analysis was conducted in laryngeal, oropharyngeal, and oral cavity squamous cell carcinoma (LSCC, OPSCC, and OCSCC).ResultsThe role of IL-33 in HNSCC was heterogeneous among tumors at different sites. In LSCC, IL-33 may increase the extent of malignancy of tumor cells and act as a pro-tumor factor. In OCSCC, IL-33 may play a role in orchestrating the immune responses against tumor cells and act as an antitumor factor. The role of IL-33 in OPSCC was undetermined. IL-33 in LSCC was mainly derived from endothelial cells, while IL-33 in OCSCC was mainly derived from endothelial and epithelial cells.ConclusionAccording to the different sources of IL-33 in LSCC and OCSCC, we propose a hypothesis that stroma-derived IL-33 could favor tumor progression, while epithelial-derived IL-33 could favor antitumor immune responses in HNSCC.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease that originates in the epithelial cells of the mucosal linings of the upper aerodigestive tract [1]
We aimed to explore the role of IL-33 in HNSCC using mRNA-seq data from The Cancer Genome Atlas (TCGA) and to better understand its potential as a biomarker or therapeutic target in HNSCC
We found that 3 types of immune cells (TH1 cells, T helper 2 (TH2) cells, and basophils) accumulated more in low IL-33 tumors than in high IL-33 tumors, while 11 types of immune cells (CD4+ T cells, naïve CD4+ T cells, Treg cells, CD8+ T cells, monocytes, dendritic cells (DCs), macrophages, M1 macrophages, neutrophils, eosinophils, and mast cells) accumulated more in high IL-33 tumors than low IL
Summary
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease that originates in the epithelial cells of the mucosal linings of the upper aerodigestive tract (oral cavity, oropharynx, hypopharynx, or larynx) [1]. Interleukin-33 (IL-33), a member of the IL-1 family, is constitutively expressed at high levels in the nuclei of various cell types, including endothelial, epithelial and fibroblastlike cells [7]. IL-33 was first described as an inducer of type 2 immune responses that activates T helper 2 (TH2) cells and mast cells [8]. IL-33 has been proven to stimulate many other immune cells, including group 2 innate lymphoid cells (ILC2s) [10], regulatory T (Treg) cells [11], T helper 1 (TH1) cells [12], CD8+ T cells [13], natural killer (NK) cells [14], dendritic cells (DCs) [15], eosinophils, basophils [16] and macrophages [17]. Due to its pleiotropic effects, IL-33 plays an important role in tissue homeostasis, infection, inflammation and cancer [7]
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