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Malignant mesothelioma (MM) is a cancer with a high mortality rate and limited therapeutic options, typically presenting as a tumor in the serous membranes, most frequently in the pleura and the peritoneum rather than in the pericardium. There is much evidence that the immune system contributes to the biogenesis, growth and metastasis of MM through the unbalanced production of oxidants and cytokines, mesothelial cell DNA damage and the active support of MM neoangiogenesis and immunosuppression. Because classical therapeutic approaches are generally ineffective, novel immunological tools are being developed to target the immune cells infiltrating the MM foci and exploit the immune system to elicit an effective anti-tumor response. These therapies work by stimulating local inflammatory cells or transferring exogenously activated immunocompetent cells and by depleting MM-associated immunosuppressive clones to target the spontaneous specific immune responses against MM and to subvert MM-driven immunoediting. This review summarizes the recent evidence on the immune system mechanisms that support MM development and the novel therapeutic approaches for strengthening the immune system by MM immunotherapy that are currently being developed in both experimental models and clinical trials., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Malignant mesothelioma (MM) is a highly fatal tumor arising from inner body membranes, whose extensive growth is facilitated by its week immunogenicity and by its ability to blunt the immune response which should arise from the huge mass of leukocytes typically infiltrating this tumor. It has been reported that the inflammatory infiltrate found in MM tissues is characterized by a high prevalence of macrophages. Thus, in this work we evaluated the ability of human MM cells to modulate the inflammatory phenotype of human THP-1 monocytes and macrophages, a widely used in vitro model of monocyte/macrophage differentiation. Furthermore, we tested the hypothesis that the exposure to MM cells could alter the differentiation of THP-1 monocytes favoring the development of alternatively activated, tumor-supporting macrophages. Our data prove for the first time that MM cells can polarize monocytes towards an altered inflammatory phenotype and macrophages towards an immunosuppressive phenotype. Moreover, we demonstrate that monocytes cocultivated with MM cells 'keep a memory' of their encounter with the tumor which influences their differentiation to macrophages. On the whole, we provide evidence that MM cells exert distinct, cell-specific effects on monocytes and macrophages. The thorough characterization of such effects may be of a crucial importance for the rational design of new immunotherapeutic protocols.

Malignant mesothelioma (MM) is a highly fatal tumor of inner body membranes, the extensive growth of which is supported by both a weak immunogenicity and the ability to reprogram surrounding immune cells towards tumor-supporting phenotypes. Interleukin-17 (IL-17) is a major inflammatory cytokine which is now accepted as the paradigmatic cytokine of many autoimmune diseases; however, its role in tumor immunology has only been partially unraveled, and no data exist regarding its possible involvement in MM. Thus, in this work we evaluated the ability of MM to induce IL-17 production in immune cells and the effects of IL-17 on MM growth and invasiveness. Our data show for the first time that macrophages and CD4+ T-cells are polarized by MM to produce IL-17, and that this cytokine exerts multiple tumor-supporting effects on both cell growth and invasiveness. These data provide novel evidence of the crosstalk occurring between MM and immune cells and suggest potential targets for the development of new pharmacological approaches for MM treatment. [ABSTRACT FROM AUTHOR]