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      Biomarkers for Malignant Pleural Mesothelioma—A Novel View on Inflammation

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          Abstract

          Simple Summary

          In view of the recent advances in immunoncology, we want to reevaluate and summarize the role of the immune system in malignant pleural mesothelioma (MPM). MPM is an aggressive disease with limited treatment options and devastating prognosis. Exposure to asbestos and chronic inflammation have long been acknowledged as main risk factors. In this review, we summarize the current knowledge about local and systemic inflammation promoting pathogenesis and progression of MPM. We focus on the prognostic and predictive value of infiltrating immune cells within the tumor and its microenvironment as local inflammation on the one hand and systemic inflammatory parameters on the other. We found that suppression of the specific and activation of the unspecific immune system are essential drivers of MPM, resulting in poor patient outcome. Numerous local and systemic inflammatory parameters are promising potential biomarkers for MPM, worth further research.

          Abstract

          Malignant pleural mesothelioma (MPM) is an aggressive disease with limited treatment response and devastating prognosis. Exposure to asbestos and chronic inflammation are acknowledged as main risk factors. Since immune therapy evolved as a promising novel treatment modality, we want to reevaluate and summarize the role of the inflammatory system in MPM. This review focuses on local tumor associated inflammation on the one hand and systemic inflammatory markers, and their impact on MPM outcome, on the other hand. Identification of new biomarkers helps to select optimal patient tailored therapy, avoid ineffective treatment with its related side effects and consequently improves patient’s outcome in this rare disease. Additionally, a better understanding of the tumor promoting and tumor suppressing inflammatory processes, influencing MPM pathogenesis and progression, might also reveal possible new targets for MPM treatment. After reviewing the currently available literature and according to our own research, it is concluded that the suppression of the specific immune system and the activation of its innate counterpart are crucial drivers of MPM aggressiveness translating to poor patient outcome.

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          Most cited references196

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Inflammation and cancer.

            Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.
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              Cancer-related inflammation.

              The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                06 February 2021
                February 2021
                : 13
                : 4
                : 658
                Affiliations
                Department of General and Thoracic Surgery, Karl Landsteiner University of Health Sciences, University Hospital Krems, 3500 Krems an der Donau, Austria; melanie.vogl@ 123456krems.lknoe.at (M.V.); arosenmayr@ 123456gmail.com (A.R.); bohanest@ 123456gmail.com (T.B.); axel.scheed@ 123456krems.lknoe.at (A.S.); milos.brndiar@ 123456krems.lknoe.at (M.B.); elisabeth.stubenberger@ 123456krems.lknoe.at (E.S.)
                Author notes
                [* ]Correspondence: bahil.ghanim@ 123456kl.ac.at ; Tel.: +43-2732-9004-4294
                Author information
                https://orcid.org/0000-0002-5634-5417
                https://orcid.org/0000-0002-6563-5643
                Article
                cancers-13-00658
                10.3390/cancers13040658
                7916017
                33562138
                3da45f62-9be2-4347-bcb5-da7e0cdb4560
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 December 2020
                : 02 February 2021
                Categories
                Review

                malignant pleural mesothelioma,inflammation,infiltrating immune cells,prognostic biomarker,predictive biomarker,immune therapy

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