Frontiers in Immunology (Apr 2024)
Autoimmunity in thymic epithelial tumors: a not yet clarified pathologic paradigm associated with several unmet clinical needs
- Matteo Perrino,
- Emanuele Voulaz,
- Emanuele Voulaz,
- Simone Balin,
- Gerardo Cazzato,
- Elena Fontana,
- Elena Fontana,
- Sara Franzese,
- Sara Franzese,
- Martina Defendi,
- Martina Defendi,
- Fabio De Vincenzo,
- Nadia Cordua,
- Roberto Tamma,
- Federica Borea,
- Federica Borea,
- Marta Aliprandi,
- Marta Aliprandi,
- Marco Airoldi,
- Marco Airoldi,
- Luigi Giovanni Cecchi,
- Luigi Giovanni Cecchi,
- Roberta Fazio,
- Roberta Fazio,
- Marco Alloisio,
- Marco Alloisio,
- Giuseppe Marulli,
- Giuseppe Marulli,
- Armando Santoro,
- Armando Santoro,
- Luca Di Tommaso,
- Luca Di Tommaso,
- Giuseppe Ingravallo,
- Laura Russo,
- Giorgio Da Rin,
- Anna Villa,
- Anna Villa,
- Silvia Della Bella,
- Silvia Della Bella,
- Paolo Andrea Zucali,
- Paolo Andrea Zucali,
- Domenico Mavilio,
- Domenico Mavilio
Affiliations
- Matteo Perrino
- Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy
- Emanuele Voulaz
- Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Milan, Italy
- Emanuele Voulaz
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Simone Balin
- Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy
- Gerardo Cazzato
- Section of Pathology, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, Bari, Italy
- Elena Fontana
- Istituto di Ricerca Genetica e Biomedica (IRGB), National Research Council (CNR), Milan, Italy
- Elena Fontana
- Human Genome and Biomedical Technologies Unit, IRCCS Humanitas Research Hospital, Milan, Italy
- Sara Franzese
- Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy
- Sara Franzese
- Unit of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
- Martina Defendi
- Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy
- Martina Defendi
- Unit of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
- Fabio De Vincenzo
- Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy
- Nadia Cordua
- Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy
- Roberto Tamma
- Section of Human Anatomy and Histology, Department of Translational Biomedicine and Neurosciences (DiBraiN), University of Bari “Aldo Moro”, Bari, Italy
- Federica Borea
- Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy
- Federica Borea
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Marta Aliprandi
- Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy
- Marta Aliprandi
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Marco Airoldi
- Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy
- Marco Airoldi
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Luigi Giovanni Cecchi
- Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy
- Luigi Giovanni Cecchi
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Roberta Fazio
- Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy
- Roberta Fazio
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Marco Alloisio
- Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Milan, Italy
- Marco Alloisio
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Giuseppe Marulli
- Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Milan, Italy
- Giuseppe Marulli
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Armando Santoro
- Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy
- Armando Santoro
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Luca Di Tommaso
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Luca Di Tommaso
- 0Department of Pathology, IRCCS Humanitas Research Hospital, Milan, Italy
- Giuseppe Ingravallo
- Section of Pathology, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, Bari, Italy
- Laura Russo
- 1Clinical Laboratory, IRCCS Humanitas Research Hospital, Milan, Italy
- Giorgio Da Rin
- 1Clinical Laboratory, IRCCS Humanitas Research Hospital, Milan, Italy
- Anna Villa
- Istituto di Ricerca Genetica e Biomedica (IRGB), National Research Council (CNR), Milan, Italy
- Anna Villa
- 2San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy
- Silvia Della Bella
- Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy
- Silvia Della Bella
- Unit of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
- Paolo Andrea Zucali
- Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy
- Paolo Andrea Zucali
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Domenico Mavilio
- Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy
- Domenico Mavilio
- Unit of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
- DOI
- https://doi.org/10.3389/fimmu.2024.1288045
- Journal volume & issue
-
Vol. 15
Abstract
Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against “self”. In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma. This comorbidity, in addition to negatively affecting the quality and duration of patients’ life, reduces the spectrum of the available therapeutic options. Indeed, the presence of autoimmunity represents an exclusion criteria for the administration of the newest immunotherapeutic treatments with checkpoint inhibitors. The pathophysiological correlation between TETs and autoimmunity remains a mystery. Several studies have demonstrated the presence of a residual and active thymopoiesis in adult patients affected by thymomas, especially in mixed and lymphocytic-rich thymomas, currently known as type AB and B thymomas. The aim of this review is to provide the state of art in regard to the histological features of the different TET histotype, to the role of the different immune cells infiltrating tumor microenvironments and their impact in the break of central immunologic thymic tolerance in thymomas. We discuss here both cellular and molecular immunologic mechanisms inducing the onset of autoimmunity in TETs, limiting the portfolio of therapeutic strategies against TETs and greatly impacting the prognosis of associated autoimmune diseases.
Keywords
