Comprehensive Analysis of Myeloid Signature Genes in Head and Neck Squamous Cell Carcinoma to Predict the Prognosis and Immune Infiltration.

Zhifeng Liu,Fengyu Zhang,Huihong Chen,Diekuo Zhang,Xin Zhang,Yong Liu,Chao Liu,Donghai Huang,Hang Ling,Xingwei Wang,Guo Li

doi:10.3389/fimmu.2021.659184

Abstract

Myeloid cells are a major heterogeneous cell population in the tumor immune microenvironment (TIME). Imbalance of myeloid response remains a major obstacle to a favorable prognosis and successful immune therapy. Therefore, we aimed to construct a risk model to evaluate the myeloid contexture, which may facilitate the prediction of prognosis and immune infiltration in patients with head and neck squamous cell carcinoma (HNSCC). In our study, six myeloid signature genes (including CCL13, CCR7, CD276, IL1B, LYVE1 and VEGFC) analyzed from 52 differentially expressed myeloid signature genes were finally pooled to establish a prognostic risk model, termed as myeloid gene score (MGS) in a training cohort and validated in a test cohort and an independent external cohort. Furthermore, based on the MGS subgroups, we were able to effectively identify patients with a poor prognosis, aggressive clinical parameters, immune cell infiltration status and immunotherapy response. Thus, MGS may serve as an effective prognostic signature and predictive indicator for immunotherapy response in patients with HNSCC.

Highlights

The tumor immune microenvironment (TIME) has an enormous impact on carcinogenesis, metastasis and progression [1, 2]
myeloid gene score (MGS) of each sample was calculated with the following equation: Risk score (MGS) = CCL13 ∗ 0.0380 + CCR7 ∗ (−0.1049) + CD276 ∗ 0.0073 + IL1B ∗ 0.0034 + LYVE1 ∗ 0.0673 + VEGFC ∗ 0.0020
According to the median value of MGS (0.246), head and neck squamous cell carcinoma (HNSCC) patients in the The Cancer Genome Atlas (TCGA) training and test cohorts were classified into MGSlow and MGShigh subgroups

Summary

Introduction

The tumor immune microenvironment (TIME) has an enormous impact on carcinogenesis, metastasis and progression [1, 2]. Diverse immune cells in TIME have conflicting effects, tumorantagonizing in some cases and tumor-promoting in others [3]. The heterogeneity of immune components is a pivotal factor affecting the interactions between tumor and TIME [4]. Increasing evidence revealed that myeloid cells are central compartments of immunosuppressive cells, as a major obstacle to immune therapy [6, 9]. Programmed death-ligand 1 (PDL1) expression on myeloid cells hampers T cells differentiation into tumor scavenging effector cells [10] and antagonizes the response to anti-PD-1 therapy [11]

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