Abstract
Although mesothelioma is the consequence of a protracted immune response to asbestos fibers and characterized by a clear immune infiltrate, novel immunotherapy approaches show less convincing results as compared to those seen in melanoma and non-small cell lung cancer. The immune suppressive microenvironment in mesothelioma is likely contributing to this therapy resistance. Therefore, it is important to explore the characteristics of the tumor microenvironment for explanations for this recalcitrant behavior. This review describes the stromal, cytokine, metabolic, and cellular milieu of mesothelioma, and attempts to make connection with the outcome of immunotherapy trials.
Highlights
Malignant pleural mesothelioma (MPM) has a justified reputation for being resistant to therapy
While this review focuses on the immune aspects of tumor microenvironment, it is prudent to acknowledge that angiogenesis is a simultaneous and interlinked process that requires therapeutic intervention
While checkpoint inhibition represents an exciting development in the treatment of several solid tumors, the outcomes in mesothelioma have been less positive and may well be affected by the complex structure of the tumor microenvironment in mesothelioma
Summary
Malignant pleural mesothelioma (MPM) has a justified reputation for being resistant to therapy. When comparing mesothelioma tissue and cell lines, we can conclude that stromal cells and cancer-associated fibroblasts or fibrocytes contribute some of the signals seen in these RNA analyses [25]. These molecules are detected in pleural effusions of patients with mesothelioma [37] and as such cancer-associated fibroblasts may contribute to the recruitment and differentiation of immunosuppressive cells.
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