TNF Patterns and Tumor Microenvironment Characterization in Head and Neck Squamous Cell Carcinoma.

Qian Long,Xiaonan Wang,Yizhuo Li,Wuguo Deng,Jin Peng,Xiang Qi,Wancui Zhu,Ankui Yang,Xiangdong Xu,Miao Chen,Dingfu Du,Chunyu Huang,Qi Meng,Fan Yao,Dingbo Shi

doi:10.3389/fimmu.2021.754818

Abstract

BackgroundHNSCC is a heterogeneous disease, which arises from distinct anatomic subsites, associates with various risk factors and possesses diverse molecular pathological features. Generally, HNSCC is considered as an immunosuppressive disease, characterized by abnormal tumor immune microenvironment. The TNF family plays a crucial role in the survival, proliferation, differentiation, and effector functions in both immune and non-immune cells. However, the expression patterns of TNF in HNSCC remains to be systematically analyzed.MethodsWe downloaded transcriptional profile data of HNSCC from TCGA and GEO datasets. Unsupervised clustering methods were used to identify different TNF patterns and classify patients for further analysis. PCA was conducted to construct a TNF relevant score, which we called risk score.ResultsIn this study, we systematically evaluated the patterns of TNF family and tumor immune microenvironment characteristics of HNSCC patients by clustering the expression of 46 members of TNF family. We identified two subtypes with distinct clinical and immune characteristics in HNSCC and constructed a risk scoring system based on the expression profile of TNF family genes.ConclusionRisk score serves as a reliable predictor of overall survival, clinical characteristics, and immune cell infiltration, which has the potential to be applied as a valuable biomarker for HNSCC immunotherapy.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors worldwide [1, 2]
We systematically evaluated the patterns of TNF family and tumor immune microenvironment characteristics of HNSCC patients by clustering the expression of 46 members of TNF family
We identified two subtypes with distinct clinical and immune characteristics in HNSCC and constructed a risk scoring system based on the expression profile of TNF family genes

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors worldwide [1, 2]. The TNF family, which consists of a 19 TNF ligand superfamily (TNFSF) and a 29 TNF receptor superfamily (TNFRSF), plays a crucial role in the survival, proliferation, differentiation, and effector functions in both immune and nonimmune cells [7]. Because of the vital role TNF family activities in inflammatory responses regulation, antagonists targeting this signaling to reduce chronic inflammation or promote anti-tumor immunity have been developed, and tested or being tested in clinical trials for inflammatory diseases or cancer [9]. In the context of head and neck cancer, TNF signaling was a well-established tumorpromoting pathway via either helping tumor cell resist apoptosis or inducing an immune suppressive tumor microenvironment [10,11,12,13,14]. The TNF family plays a crucial role in the survival, proliferation, differentiation, and effector functions in both immune and non-immune cells. The expression patterns of TNF in HNSCC remains to be systematically analyzed

Methods

Results

Conclusion