Comprehensive characterization of the tumor microenvironment for assessing immunotherapy outcome in patients with head and neck squamous cell carcinoma.

Jian Zhang,Hualong Jiang,Yunhong Tian,Yawei Yuan,Baiyao Wang,Tao Xie,Xi Zhong,Rong Li,Huali Jiang,Jiexia Zhang

doi:10.18632/aging.103460

Abstract

The tumor microenvironment (TME) constitutes a complex milieu of cells and cytokines that maintain equilibrium between tumor progression and prognosis. However, comprehensive analysis of the TME and its clinical significance in head and neck squamous cell carcinoma (HNSCC) remains to be unreported. In this study, based on large-scale RNA sequencing data pertaining to single nucleotide variants (SNVs) and copy number variations (CNVs) in HNSCC patients from The Cancer Genome Atlas database, we analysed subpopulations of infiltrating immune cells and evaluated the role of TME infiltration pattern (TME score) in assessing immunotherapy outcome. TME signature genes involved in several inflammation and immunity signalling pathways were observed in the TME score subtype, which were considered immunosuppressive and potentially responsible for significantly worse prognosis. In comparison with SNV- and CNV-mediated tumor mutation burden, TME score can significantly differentiate between high- and low-risk HNSCC and predict immunotherapy outcome. Our data provide clarity on the comprehensive landscape of interactions between clinical characteristics of HNSCC and tumor-infiltrating immune cells. TME score seems to be a useful biomarker that can predict immunotherapy outcome in HNSCC patients.

Highlights

Head and neck squamous cell carcinoma (HNSCC), one of most common cancers in the world, is an aggressive and frequently lethal head and neck malignancy [1]
To investigate tumor microenvironment (TME) characteristics in HNSCC, based on the RNA sequencing (RNA-seq) data of 502 patients with HNSCC from The Cancer Genome Atlas (TCGA) database, we systematically investigated 22 subpopulations of infiltrating immune cells using CIBERSORT
The distribution ratio of infiltrating immune cells among the samples showed a significant difference (Figure 1A), and the TME cell network depicted a comprehensive landscape of tumor–immune cell interactions, cell lineages and their effects on the overall survival (OS) of patients with HNSCC (Figure 1B; Supplementary Table 1)

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC), one of most common cancers in the world, is an aggressive and frequently lethal head and neck malignancy [1]. Despite advances in diagnostic and therapeutic approaches, the 5-year survival rate of patients with HNSCC is only approximately 50%–60% [2]. HNSCC www.aging-us.com is associated with distinct clinical and biological heterogeneity; patients with aggressive disease are managed using cetuximab, an anti-EGFR antibody, but only around 13% metastatic patients respond to such treatment [3, 4]. Phase III clinical trials of programmed death (PD)-1 immune checkpoint inhibitors (ICIs) (pembrolizumab and nivolumab) and PD-ligand (L) (durvalumab and avelumab) ICI immunotherapy have been performed in patients with recurrent and metastatic HNSCC. Pembrolizumab combined with platinum and fluorouracil was found to outperform the cetuximabbased platinum and fluorouracil combination in terms of overall survival (median, 13.6 vs 10.1 months) when administered as the first-line of treatment for recurrent and metastatic HNSCC. Little is known about mechanisms underlying the response of patients with HNSCC to immunotherapy

Methods

Results

Conclusion