The Immune Microenvironment of Malignant Pleural Mesothelioma: A Literature Review

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour with a poor prognosis, associated with asbestos exposure. Nowadays, treatment is based on chemotherapy with a median overall survival of less than two years. This review highlights the main characteristics of the immune microenvironment in MPM with special emphasis on recent biological advances. The MPM microenvironment is highly infiltrated by tumour-associated macrophages, mainly M2-macrophages. In line with infiltration by M2-macrophages, which contribute to immune suppression, other effectors of innate immune response are deficient in MPM, such as dendritic cells or natural killer cells. On the other hand, tumour infiltrating lymphocytes (TILs) are also found in MPM, but CD4+ and CD8+ TILs might have decreased cytotoxic effects through T-regulators and high expression of immune checkpoints. Taken together, the immune microenvironment is particularly heterogeneous and can be considered as mainly immunotolerant or immunosuppressive. Therefore, identifying molecular vulnerabilities is particularly relevant to the improvement of patient outcomes and the assessment of promising treatment approaches.

Mesothelioma Malignancy and the Microenvironment: Molecular Mechanisms

“…Failed phagocytosis of asbestos fibers by macrophages represents one of the possible mechanisms promoting neoplastic transformation of mesothelial cells [ 79 ]. Phagocytic macrophages, unable to eliminate fibers, release oxidative molecules and pro-inflammatory cytokines that promote a pro-inflammatory environment and activate signaling pathways in tumor cells that help them to survive despite the asbestos-related damage [ 80 ]. A critical pro-inflammatory mediator in the mesothelial transformation process has been identified in high-mobility group protein box 1 (HMGB1), a cytokine that, upon asbestos exposure, is released by mesothelial cells recruiting and activating macrophages.…”

Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach

“…Every tumor (and, thus, MPM) is made with malignant cells plus stroma: the main and specific issue is related to the role played by asbestos (rather than activation of specific oncogenes) in both driving malignant transformation and modulating tumors surrounding stroma [2,12]. Although a deep description of MPM surrounding stroma goes beyond the scope of this review and can be available in detail in recently published literature, e.g., [2,[12][13][14][15], it is relevant to underline that the chronic inflammatory response to asbestos leads to the generation of a specific and heterogeneous stroma which sustains malignant transformation [16]. In detail, it determines an increased production of reactive oxygen species (ROS) and free radicals which recall inflammatory cells [17,18].…”

Inflammation of the Pleural Cavity: A Review on Pathogenesis, Diagnosis and Implications in Tumor Pathophysiology

“…Malignant pleural effusion is associated with poor prognosis showing a median overall survival of 11 months depending on histological type and performance status [4]. Furthermore, even in this advanced tumoral setting, the inflammatory nature of malignant effusions significantly impacts on prognosis [3,5], whereas achieving pleurodesis in malignant pleural effusion also imparts a survival benefit in these patients [6], but through unknown mechanisms. On the other hand, non-malignant etiologies explain most pleural effusions and understanding the key events of benign pleural pathologies is important to better treat these patients [7].…”