Systemic Immune Dysregulation Correlates With Clinical Features of Early Non-Small Cell Lung Cancer.

Zhixing Hao,Ying Chai,Pin Wu,Mingjie Lin,Wenshan Li,Yimin Wu,Feng Du,Qun Yu,Shenghang Jin,Zhongwei Xin,Zhouyu Zhu,Yongyuan Chen,Xiaoke Chen,Dang Wu

doi:10.3389/fimmu.2021.754138

Zhixing Hao, Ying Chai + Show 12 more

Open Access

https://doi.org/10.3389/fimmu.2021.754138

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Abstract

BackgroundSystemic immune dysregulation correlates with cancer progression. However, the clinical implications of systemic immune dysregulation in early non-small cell lung cancer (NSCLC) remain unclear.MethodsUsing a panel of 9 markers to identify 12 parameters in the peripheral blood of 326 patients (34 in the discovery group and 292 in the validation group), we investigated systemic immune dysregulation in early NSCLC. Then, we analyzed the impact of surgery on the systemic immune state of these patients. Finally, we analyzed correlations between systemic immune dysregulation and the clinical features of early NSCLC.ResultsWe found striking systemic immune dysregulation in the peripheral blood of early NSCLC patients. This dysregulation was characterized by a significant decrease in total lymphocytes, T cells, quiescent T cells, CD4+ T cells, and NKT cells. We also observed increased proportions of activated lymphocytes and activated T cells. Systemic immune dysregulation was increased after surgery. Furthermore, systemic immune dysregulation was correlated with multiple clinical features, such as sex, age, smoking history, pathological type, tumor stage, surgical approach, tumor differentiation, and epidermal growth factor receptor (EGFR) mutation. Finally, we observed that systemic immune dysregulation was correlated with complications and systemic inflammatory response syndrome (SIRS) in early NSCLC patients.ConclusionsOur results reveal systemic immune dysregulation occurring in early NSCLC and demonstrate the correlation between these dysregulations and clinical features. Our findings suggest that systemic immune dysregulation is involved in cancer development and may be a promising candidate for high-risk screening and treatment strategies for early NSCLC.

Highlights

Non-small cell lung cancer (NSCLC) is a common cancer type that leads to morbidity and mortality worldwide [1]
Our study found an observable change in the immune state of early NSCLC patients with respect to systemic immune dysregulation, which correlated with clinical features such as gender, age, and tumor stage
We first profiled the leukocyte subsets in the peripheral blood (PB) of 34 healthy donors and 34 preoperative patients with early NSCLC who were subsequently pathologically confirmed

Summary

Introduction

Non-small cell lung cancer (NSCLC) is a common cancer type that leads to morbidity and mortality worldwide [1]. A recent study showed that resident immune cells in preinvasive lesions became dysfunctional in the early stages of human lung squamous carcinogenesis [5]. Another single-cell study showed that the tumor-infiltrating myeloid cell subsets change during the early stages of human lung adenocarcinoma (LUAD) [6]. Another study found that most dysfunctional TILs show resident immune cell features [9, 10] These findings suggest an unexpected phenomenon in which local immune perturbation in the tumor microenvironment occurs as early as during the initiation stage of human NSCLC [11]. The clinical implications of systemic immune dysregulation in early non-small cell lung cancer (NSCLC) remain unclear

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