Comprehensive Characterization of Immune Landscape Based on Epithelial-Mesenchymal Transition Signature in OSCC: Implication for Prognosis and Immunotherapy.

Xian-Yue Ren,Wei-Lin Zhang,Tong Wu,Chun-Yang Wang,Ruo-Yan Cao,Bin Cheng,Si-Yuan Zhang,Jia-Ying Zhou,Xue Pan,Xin-Ran Tang,Qin Liu,Xi-Juan Chen

doi:10.3389/fonc.2021.587862

Xian-Yue Ren, Wei-Lin Zhang + Show 10 more

Open Access

https://doi.org/10.3389/fonc.2021.587862

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Abstract

Current anatomic TNM stage classification fails to capture the immune heterogeneity of oral squamous cell carcinoma (OSCC). Increasing evidence indicates the strong association between epithelial-mesenchymal transition (EMT) and tumor immune response. In this study, we employed an EMT signature to classify OSCC patients into epithelial- (E-) and mesenchymal- (M-) phenotypes using TCGA and GSE41613 transcriptome data. The ESTIMATE and CIRBERSORT analyses implied that the EMT signature genes originated from the stroma of the bulk tissue. The M-subtype tumors were characterized as “immune-hot” with more immune cell infiltration than the E-subtype ones. The low infiltration of active immune cells, the high infiltration of inactive immune cells, and the high expressions of immune checkpoints demonstrated an immunosuppressive characteristic of the M-subtype tumors. Moreover, we developed and validated a novel prognostic classifier based on the EMT score, the expressions of seven immune checkpoints, and the TNM stages, which could improve the prediction efficiency of the current clinical parameter. Together, our findings provide a better understanding of the tumor immune heterogeneity and may aid guiding immunotherapy in OSCC.

Highlights

Oral squamous cell carcinoma (OSCC), arising from the mucosal lining of the buccal mucosa, floor of the mouth, tongue, and other parts within the oral cavity, is a heterogeneous subgroup of head and neck squamous cell carcinoma (HNSC) [1, 2]
Biological process indicated that the differentially expressed genes (DEGs) were significantly associated with collagen, integrin glycosaminoglycan binding, and extracellular structural constituent, while molecules function analysis implied that DEGs were enriched in matrix structural constitute, integrin binding, and extracellular matrix structure (Figures 2C, D and Supplementary Figure 2)
Accumulating evidence has demonstrated that cancer patients with an endogenous immune response that coexists with immune checkpoint elevation might be sensitive to the immune checkpoint agents

Summary

Introduction

Oral squamous cell carcinoma (OSCC), arising from the mucosal lining of the buccal mucosa, floor of the mouth, tongue, and other parts within the oral cavity, is a heterogeneous subgroup of head and neck squamous cell carcinoma (HNSC) [1, 2]. Patients with advanced OSCC received platinum-based chemotherapy and best supportive care. Prognostic definition and EMT in OSCC immune activity treatment decisions of OSCC patients are mainly dependent on the tumor-node-metastasis (TNM) classification. Only 50% of patients are expected to survive over five years and continue to have a very poor prognosis [2, 3]. The current anatomical-based staging system is not sufficient to select patients at high risk of treatment failure. Identifying the novel biomarkers which can reflect tumor heterogeneity is still a challenge

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