Immune Cell Subtypes and Cytokines in Lung Tumor Microenvironment: Influence of COPD.

Jun Tang,Víctor Curull,Xavier Duran,Xuejie Wang,Mercé Mateu-Jiménez,Alberto Rodríguez-Fuster,Daniel Ramis-Cabrer,Lara Pijuan,Esther Barreiro,Liyun Qin,Rafael Aguiló Espases

doi:10.3390/cancers12051217

Abstract

Background: The immune microenvironment plays a role in tumorigenesis. Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for lung cancer (LC). We hypothesized that immune profile characterized by T regulatory (Treg), natural killer (NK), and plasma cells, as well as interleukin (IL)-10 and interferon-gamma, may differ within tumors of LC patients with/without COPD. Methods: Treg (anti-CD3 and anti-forkhead boxP3 antibodies), NK (anti-NCR1 antibody), IgG (anti-CD138-IgG antibody), IgA (anti-CD138-IgA antibody) using immunohistochemistry, and both IL-10 and interferon-gamma (ELISA) were quantified in tumor and non-tumor specimens (thoracotomy for lung tumor resection) from 33 LC–COPD patients and 20 LC-only patients. Results: Immune profile in tumor versus non-tumor specimens: Treg cell counts significantly increased in tumors of both LC and LC–COPD patients, while in tumors of the latter group, IgG-secreting plasma cells significantly decreased and IL-10 increased. No significant differences were seen in levels of NK cells, IgA-secreting cells, IgA/IgG, or interferon-gamma. Immune profile in tumors of LC–COPD versus LC: No significant differences were observed in tumors between LC–COPD and LC patients for any study marker. Conclusions: Immune cell subtypes and cytokines are differentially expressed in lung tumors, and the presence of COPD elicited a decline in IgG-secreting plasma cell levels but not in other cell types.

Highlights

Lung cancer (LC) continues to be a major cause of mortality worldwide [1,2,3,4,5]
Age did not significantly differ between the two groups of patients, while body mass index (BMI) was significantly lower in lung cancer (LC)–Chronic Obstructive Pulmonary Disease (COPD) patients compared to LC patients
Current smokers and the number of pack/year was significantly greater in lung cancer–Chronic Obstructive Pulmonary Disease (LC–COPD) patients compared to LC patients, while the number of never smokers was significantly greater in the latter group (Table 1)

Summary

Introduction

Lung cancer (LC) continues to be a major cause of mortality worldwide [1,2,3,4,5]. In certain geographical areas, LC may account for up to one-third of deaths [1,2,3,4,5,6]. COPD more susceptible to the development of emphysema remain to be fully elucidated Several biological events such as increased oxidative stress, inflammation, epigenetics, and tumor microenvironment have been proposed as mechanisms that underlie the process of tumorigenesis in patients with chronic airway obstruction and emphysema [7,18]. Those events interact with key cellular mechanisms, such as angiogenesis, cell repair, and cell death and growth, which may interfere with cell survival, promoting tumorigenesis and LC development [7,19]. No significant differences were seen in levels of NK cells, IgA-secreting cells, IgA/IgG, or interferon-gamma

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