Abstract
The tumor microenvironment (TME) is significantly associated with clinical outcomes and therapeutic efficacy. However, the landscape of the head and neck cancer (HNC) microenvironment is not fully understood. Therefore, we divided HNCs into three classes according to differences in the TME to determine effective personalized treatments. We explored the immune landscape of head and neck cancer by analysing the gene expression profile of 501 cases from the Cancer Genome Atlas (TCGA) data portal and validated our findings in 270 cases from the Gene Expression Omnibus (GEO) database. The levels of immune components in the tumor microenvironment were evaluated via single-sample gene set enrichment (ssGSEA) analysis. The HNCs were clustered into an Immunity-H group, Immunity-M group and Immunity-L group according to 40 immune components in the tumor microenvironment. DNA damage and HLA genes play an important role in immune regulation. The patients in the Immunity-H group had a favourable survival compared with patients in the Immunity-M group and the Immunity-L group. The patients in the Immunity-H group and Immunity-M group could benefit from radiotherapy. In addition, the Immunity-L group showed the lowest immunophenoscore and had poor response to anti-PD-1 treatment. CXCR3 was demonstrated to be downregulated in the Immunity-L group, which was related to shorter OS in the TCGA and GEO databases, suggesting CXCR3 as a potential therapeutic target. Taken together, our findings proposed three new microenvironment-related phenotypes of HNCs and suggested that CXCR3 played a major role in immune regulation and could be a novel therapeutic target, providing a reference for clinical decisions and research directions in the future.
Highlights
Head and neck squamous cancer (HNSCC) ranks seventh in global cancer incidence, and 890,000 people were diagnosed with HNSCC in 2018 [1]
We evaluated the levels of 40 immune components, including immune cells, immune factors, and immune pathways, by the Single-Sample Gene Set Enrichment Analysis (ssGSEA) method according to the transcriptomes of 501 the Cancer Genome Atlas (TCGA)-HNSC patients
We demonstrated that the HNSCC samples had three different immune statuses when assessed by 40 immune components
Summary
Head and neck squamous cancer (HNSCC) ranks seventh in global cancer incidence, and 890,000 people were diagnosed with HNSCC in 2018 [1]. On the basis of traditional treatments, including surgical resection and chemoradiation, the 5-year survival rate of HNC remains 40%–50% [2]. A monoclonal antibody (mAb) targeting epidermal growth factor receptor (EGFR), no other new targeted therapies have been approved for HNSCC for decades. Cetuximab monotherapy efficiency is only 10%~15%, and there are no known biomarkers for predicting response [3, 4]. Immunotherapy has been approved by the FDA and EMEA to treat recurrent and metastatic patients with HNSCC [5]. Regardless of the type of treatment, some people do not benefit or experience associated side effects. It is crucial to explore new therapeutic targets and identify therapeutic methods that are suitable for specific groups of people
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