Immune Cell Composition in Human Non-small Cell Lung Cancer

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the world. Immunological analysis of the tumor microenvironment (immunoscore) shows great promise for improved prognosis and prediction of response to immunotherapy. However, the exact immune cell composition in NSCLC remains unclear. Here, we used flow cytometry to characterize the immune infiltrate in NSCLC tumors, non-cancerous lung tissue, regional lymph node, and blood. The cellular identity of >95% of all CD45+ immune cells was determined. Thirteen distinct immune cell types were identified in NSCLC tumors. T cells dominated the lung cancer landscape (on average 47% of all CD45+ immune cells). CD4+ T cells were the most abundant T cell population (26%), closely followed by CD8+ T cells (22%). Double negative CD4−CD8− T cells represented a small fraction (1.4%). CD19+ B cells were the second most common immune cell type in NSCLC tumors (16%), and four different B cell sub-populations were identified. Macrophages and natural killer (NK) cells composed 4.7 and 4.5% of the immune cell infiltrate, respectively. Three types of dendritic cells (DCs) were identified (plasmacytoid DCs, CD1c+ DCs, and CD141+ DCs) which together represented 2.1% of all immune cells. Among granulocytes, neutrophils were frequent (8.6%) with a high patient-to-patient variability, while mast cells (1.4%), basophils (0.4%), and eosinophils (0.3%) were less common. Across the cohort of patients, only B cells showed a significantly higher representation in NSCLC tumors compared to the distal lung. In contrast, the percentages of macrophages and NK cells were lower in tumors than in non-cancerous lung tissue. Furthermore, the fraction of macrophages with high HLA-DR expression levels was higher in NSCLC tumors relative to distal lung tissue. To make the method readily accessible, antibody panels and flow cytometry gating strategy used to identify the various immune cells are described in detail. This work should represent a useful resource for the immunomonitoring of patients with NSCLC.

Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of lung adenocarcinoma

“…Besides, the KEGG pathway enrichment displayed that the DEGs mostly clustered in the Cytokine−cytokine receptor interaction, the Chemokine signaling pathway, and the Viral protein interaction with cytokine and cytokine receptor. Consistent with these results, previous studies have shown that the biological processes of the immune system are critical to the formation of a complicated LUAD tumor microenvironment 10,30,[37][38][39] . In the past few years, the understanding of the immunological characteristics of LUAD has increased, and the development of effective LUAD immunotherapy strategies has drawn wide attention [40][41][42][43][44] .…”

“…For example, levels of immune cell infiltration have been reported to be related to prognosis, and the activity of both immune and stromal cells has been shown to predict overall cancer survival 8 . Each component of the microenvironment plays an important role in LUAD, and therefore has a significant impact on clinical outcomes 5,[9][10][11][12][13][14][15] .…”

Macrophage and Tumor Cell Cross-Talk Is Fundamental for Lung Tumor Progression: We Need to Talk

“…Currently, there is no consensus in the literature on whether the high density of macrophages is detrimental or beneficial in lung cancer, while few recent reports demonstrated the correlation between prognosis and patient survival with the density of particular phenotype of macrophages. The prolonged patient survival correlated with a high density of M1 macrophages, while poor prognosis correlated with a high density of M2 macrophages in tumor islets (14)(15)(16)(17)(18)(19). Evidences suggest that cytokines secreted by TAMs induce hyperproliferative, anti-apoptotic, and metastatic responses in lung cancer, offering a potential immunotherapeutic option for its treatment (20)(21)(22).…”

XB130, regulated by miR‐203, miR‐219, and miR‐4782‐3p, mediates the proliferation and metastasis of non‐small‐cell lung cancer cells

“…Despite advances in diagnosis and therapy, the 5‐year survival rate of patients with NSCLC has been fairly poor over the past several years. It is imperative for us to well understand the molecular mechanism of NSCLC development and progression for providing new strategies in the early diagnosis and treatment of NSCLC 1,2 …”

“…It is imperative for us to well understand the molecular mechanism of NSCLC development and progression for providing new strategies in the early diagnosis and treatment of NSCLC. 1,2 XB130, also known as actin filament associated protein 1-like 2, is a novel multifunctional adapter protein. [3][4][5] First, XB130 crosslinks actin filaments (F-actin), promoting cell endocytosis, migration, and invasion.…”