The role of myeloid-derived suppressor cells in the relationship between chronic obstructive pulmonary disease and lung cancer

Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary and systemic inflammation. There is strong evidence showing that COPD is an independent risk factor for lung cancer (LC). Chronic inflammatory response can affect all stages of tumour development, from tumour initiation to metastasis. Inflammation also alters tumour immune surveillance. Myeloid-derived suppressor cells (MDSC) are a heterogeneous mixture of immature granulocytic and monocytic cells characterized by an ability to suppress the antitumour activity of T-cells by down-regulation of the T-cell receptor chain (TCR ζ) through the catabolism of l-arginine. COPD and lung cancer share a common pattern of expansion of MDSC associated with TCR ζ downregulation and T-cell dysfunction. MDSC may impair tumour immunosurveillance in COPD and can potentially facilitate tumour initiation and growth, contributing to explain the increased incidence of lung cancer reported in these patients. Introduction Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by airflow obstruction associated with destruction of lung parenchyma caused by chronic inhalation of gases and noxious particles, primarily tobacco smoke. Comorbidities and exacerbations contribute to the severity of the disease [1]. COPD is highly prevalent and affects approximately 10% of adults worldwide [2]. It is the third most common cause of death in the United States, and it is estimated that it will be the third leading cause of death and disability worldwide by 2020 [3]. Comorbidities associated with COPD crucially influence the clinical symptoms, progress and prognosis of the disease [1]. Lung cancer is one of the most significant and common causes of death in COPD patients. Although the underlying mechanisms are not fully understood, lung cancer and COPD are clearly associated, possibly due to chronic inflammation [4-6]. Rudolf Virchow first suggested the potential link between inflammation and cancer in the 19th century. During the last decades there has been clear evidence that chronic inflammation plays a key role at every stage of tumourigenesis, from tumour initiation to tumour progression and metastatic dissemination [7]. Inflammatory cells produce a variety of molecules that can cause DNA mutations, genomic instability, malignant cell proliferation, neovascularization, invasion and metastasis. Chronic inflammation may also favour cancer development by disarming the capacity of the immune system to detect Correspondence to: Dr. Jaume Sauleda, M.D., PhD, Hospital Universitari Son Espases, C/Valldemossa 79, Planta 0, Mod. C, 07010, Palma de Mallorca, España, Spain, Tel: 871206718, Fax: 871-90.97.24, E-mail: [email protected]