Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma
Malignant pleural mesothelioma (MPM) is a rare and fatal disease of the pleural lining. Up to 80% of the MPM cases are linked to asbestos exposure. Even though its use has been banned in the industrialized countries, the cases continue to increase. MPM is a lethal cancer, with very little survival i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.660039/full |
| _version_ | 1831724082858557440 |
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| author | Stefanie Hiltbrunner Stefanie Hiltbrunner Laura Mannarino Michaela B. Kirschner Isabelle Opitz Angelica Rigutto Angelica Rigutto Alexander Laure Alexander Laure Michela Lia Paolo Nozza Antonio Maconi Sergio Marchini Maurizio D’Incalci Alessandra Curioni-Fontecedro Alessandra Curioni-Fontecedro Federica Grosso Federica Grosso |
| author_facet | Stefanie Hiltbrunner Stefanie Hiltbrunner Laura Mannarino Michaela B. Kirschner Isabelle Opitz Angelica Rigutto Angelica Rigutto Alexander Laure Alexander Laure Michela Lia Paolo Nozza Antonio Maconi Sergio Marchini Maurizio D’Incalci Alessandra Curioni-Fontecedro Alessandra Curioni-Fontecedro Federica Grosso Federica Grosso |
| author_sort | Stefanie Hiltbrunner |
| collection | DOAJ |
| description | Malignant pleural mesothelioma (MPM) is a rare and fatal disease of the pleural lining. Up to 80% of the MPM cases are linked to asbestos exposure. Even though its use has been banned in the industrialized countries, the cases continue to increase. MPM is a lethal cancer, with very little survival improvements in the last years, mirroring very limited therapeutic advances. Platinum-based chemotherapy in combination with pemetrexed and surgery are the standard of care, but prognosis is still unacceptably poor with median overall survival of approximately 12 months. The genomic landscape of MPM has been widely characterized showing a low mutational burden and the impairment of tumor suppressor genes. Among them, BAP1 and BLM are present as a germline inactivation in a small subset of patients and increases predisposition to tumorigenesis. Other studies have demonstrated a high frequency of mutations in DNA repair genes. Many therapy approaches targeting these alterations have emerged and are under evaluation in the clinic. High-throughput technologies have allowed the detection of more complex molecular events, like chromotripsis and revealed different transcriptional programs for each histological subtype. Transcriptional analysis has also paved the way to the study of tumor-infiltrating cells, thus shedding lights on the crosstalk between tumor cells and the microenvironment. The tumor microenvironment of MPM is indeed crucial for the pathogenesis and outcome of this disease; it is characterized by an inflammatory response to asbestos exposure, involving a variety of chemokines and suppressive immune cells such as M2-like macrophages and regulatory T cells. Another important feature of MPM is the dysregulation of microRNA expression, being frequently linked to cancer development and drug resistance. This review will give a detailed overview of all the above mentioned features of MPM in order to improve the understanding of this disease and the development of new therapeutic strategies. |
| first_indexed | 2024-12-21T04:14:33Z |
| format | Article |
| id | doaj.art-6ff52d24fb5a455594cd6f686950112c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-21T04:14:33Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-6ff52d24fb5a455594cd6f686950112c2022-12-21T19:16:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-06-011110.3389/fonc.2021.660039660039Tumor Immune Microenvironment and Genetic Alterations in MesotheliomaStefanie Hiltbrunner0Stefanie Hiltbrunner1Laura Mannarino2Michaela B. Kirschner3Isabelle Opitz4Angelica Rigutto5Angelica Rigutto6Alexander Laure7Alexander Laure8Michela Lia9Paolo Nozza10Antonio Maconi11Sergio Marchini12Maurizio D’Incalci13Alessandra Curioni-Fontecedro14Alessandra Curioni-Fontecedro15Federica Grosso16Federica Grosso17Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, SwitzerlandComprehensive Cancer Center Zurich, University of Zurich, Zurich, SwitzerlandDepartment of Oncology, Istituto di Ricerche Farmacologiche Mario Negri Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milano, ItalyDepartment of Thoracic Surgery, University Hospital Zurich, Zurich, SwitzerlandDepartment of Thoracic Surgery, University Hospital Zurich, Zurich, SwitzerlandDepartment of Medical Oncology and Hematology, University Hospital Zurich, Zurich, SwitzerlandComprehensive Cancer Center Zurich, University of Zurich, Zurich, SwitzerlandDepartment of Medical Oncology and Hematology, University Hospital Zurich, Zurich, SwitzerlandComprehensive Cancer Center Zurich, University of Zurich, Zurich, SwitzerlandMesothelioma Unit, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, ItalyDepartment of Pathology, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, ItalyInfrastruttura Ricerca Formazione Innovazione (IRFI), Dipartimento Attività Integrate Ricerca e Innovazione (DAIRI), Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, ItalyDepartment of Oncology, Istituto di Ricerche Farmacologiche Mario Negri Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milano, ItalyDepartment of Oncology, Istituto di Ricerche Farmacologiche Mario Negri Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milano, ItalyDepartment of Medical Oncology and Hematology, University Hospital Zurich, Zurich, SwitzerlandComprehensive Cancer Center Zurich, University of Zurich, Zurich, SwitzerlandMesothelioma Unit, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, ItalyTranslational Medicine, Dipartimento Attività Integrate Ricerca e Innovazione (DAIRI), Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, ItalyMalignant pleural mesothelioma (MPM) is a rare and fatal disease of the pleural lining. Up to 80% of the MPM cases are linked to asbestos exposure. Even though its use has been banned in the industrialized countries, the cases continue to increase. MPM is a lethal cancer, with very little survival improvements in the last years, mirroring very limited therapeutic advances. Platinum-based chemotherapy in combination with pemetrexed and surgery are the standard of care, but prognosis is still unacceptably poor with median overall survival of approximately 12 months. The genomic landscape of MPM has been widely characterized showing a low mutational burden and the impairment of tumor suppressor genes. Among them, BAP1 and BLM are present as a germline inactivation in a small subset of patients and increases predisposition to tumorigenesis. Other studies have demonstrated a high frequency of mutations in DNA repair genes. Many therapy approaches targeting these alterations have emerged and are under evaluation in the clinic. High-throughput technologies have allowed the detection of more complex molecular events, like chromotripsis and revealed different transcriptional programs for each histological subtype. Transcriptional analysis has also paved the way to the study of tumor-infiltrating cells, thus shedding lights on the crosstalk between tumor cells and the microenvironment. The tumor microenvironment of MPM is indeed crucial for the pathogenesis and outcome of this disease; it is characterized by an inflammatory response to asbestos exposure, involving a variety of chemokines and suppressive immune cells such as M2-like macrophages and regulatory T cells. Another important feature of MPM is the dysregulation of microRNA expression, being frequently linked to cancer development and drug resistance. This review will give a detailed overview of all the above mentioned features of MPM in order to improve the understanding of this disease and the development of new therapeutic strategies.https://www.frontiersin.org/articles/10.3389/fonc.2021.660039/fullmesotheliomatumor microenvironmentgenetic alterationsimmunotherapytargeted therapy |
| spellingShingle | Stefanie Hiltbrunner Stefanie Hiltbrunner Laura Mannarino Michaela B. Kirschner Isabelle Opitz Angelica Rigutto Angelica Rigutto Alexander Laure Alexander Laure Michela Lia Paolo Nozza Antonio Maconi Sergio Marchini Maurizio D’Incalci Alessandra Curioni-Fontecedro Alessandra Curioni-Fontecedro Federica Grosso Federica Grosso Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma Frontiers in Oncology mesothelioma tumor microenvironment genetic alterations immunotherapy targeted therapy |
| title | Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma |
| title_full | Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma |
| title_fullStr | Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma |
| title_full_unstemmed | Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma |
| title_short | Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma |
| title_sort | tumor immune microenvironment and genetic alterations in mesothelioma |
| topic | mesothelioma tumor microenvironment genetic alterations immunotherapy targeted therapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.660039/full |
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