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Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types
Malignant peritoneal mesothelioma (MpM), arising in the setting of local inflammation, is a rare aggressive tumour with a poor prognosis and limited therapeutic options. The three major MpM histological variants, epithelioid (E-MpMs), biphasic, and sarcomatoid MpMs (S-MpMs), are characterised by an...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231377/ https://www.ncbi.nlm.nih.gov/pubmed/30510965 http://dx.doi.org/10.1155/2018/5804230 |
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author | Tazzari, Marcella Brich, Silvia Tuccitto, Alessandra Bozzi, Fabio Beretta, Valeria Spagnuolo, Rosalin D. Negri, Tiziana Stacchiotti, Silvia Deraco, Marcello Baratti, Dario Camisaschi, Chiara Villa, Antonello Vergani, Barbara Rivoltini, Licia Pilotti, Silvana Castelli, Chiara |
author_facet | Tazzari, Marcella Brich, Silvia Tuccitto, Alessandra Bozzi, Fabio Beretta, Valeria Spagnuolo, Rosalin D. Negri, Tiziana Stacchiotti, Silvia Deraco, Marcello Baratti, Dario Camisaschi, Chiara Villa, Antonello Vergani, Barbara Rivoltini, Licia Pilotti, Silvana Castelli, Chiara |
author_sort | Tazzari, Marcella |
collection | PubMed |
description | Malignant peritoneal mesothelioma (MpM), arising in the setting of local inflammation, is a rare aggressive tumour with a poor prognosis and limited therapeutic options. The three major MpM histological variants, epithelioid (E-MpMs), biphasic, and sarcomatoid MpMs (S-MpMs), are characterised by an increased aggressiveness and enhanced levels of EZH2 expression. To investigate the MpM immune contexture along the spectrum of MpM histotypes, an extended in situ analysis was performed on a series of 14 cases. Tumour-infiltrating immune cells and their functionality were assessed by immunohistochemistry, immunofluorescence, qRT-PCR, and flow cytometry analysis. MpMs are featured by a complex immune landscape modulated along the spectrum of MpM variants. Tumour-infiltrating T cells and evidence for pre-existing antitumour immunity are mainly confined to E-MpMs. However, Th1-related immunological features are progressively impaired in the more aggressive forms of E-MpMs and completely lost in S-MpM. Concomitantly, E-MpMs show also signs of active immune suppression, such as the occurrence of Tregs and Bregs and the expression of the immune checkpoint inhibitory molecules PD1 and PDL1. This study enriches the rising rationale for immunotherapy in MpM and points to the E-MpMs as the most immune-sensitive MpM histotypes, but it also suggests that synergistic interventions aimed at modifying the tumour microenvironment (TME) should be considered to make immunotherapy beneficial for these patients. |
format | Online Article Text |
id | pubmed-6231377 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-62313772018-12-03 Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types Tazzari, Marcella Brich, Silvia Tuccitto, Alessandra Bozzi, Fabio Beretta, Valeria Spagnuolo, Rosalin D. Negri, Tiziana Stacchiotti, Silvia Deraco, Marcello Baratti, Dario Camisaschi, Chiara Villa, Antonello Vergani, Barbara Rivoltini, Licia Pilotti, Silvana Castelli, Chiara J Immunol Res Research Article Malignant peritoneal mesothelioma (MpM), arising in the setting of local inflammation, is a rare aggressive tumour with a poor prognosis and limited therapeutic options. The three major MpM histological variants, epithelioid (E-MpMs), biphasic, and sarcomatoid MpMs (S-MpMs), are characterised by an increased aggressiveness and enhanced levels of EZH2 expression. To investigate the MpM immune contexture along the spectrum of MpM histotypes, an extended in situ analysis was performed on a series of 14 cases. Tumour-infiltrating immune cells and their functionality were assessed by immunohistochemistry, immunofluorescence, qRT-PCR, and flow cytometry analysis. MpMs are featured by a complex immune landscape modulated along the spectrum of MpM variants. Tumour-infiltrating T cells and evidence for pre-existing antitumour immunity are mainly confined to E-MpMs. However, Th1-related immunological features are progressively impaired in the more aggressive forms of E-MpMs and completely lost in S-MpM. Concomitantly, E-MpMs show also signs of active immune suppression, such as the occurrence of Tregs and Bregs and the expression of the immune checkpoint inhibitory molecules PD1 and PDL1. This study enriches the rising rationale for immunotherapy in MpM and points to the E-MpMs as the most immune-sensitive MpM histotypes, but it also suggests that synergistic interventions aimed at modifying the tumour microenvironment (TME) should be considered to make immunotherapy beneficial for these patients. Hindawi 2018-10-29 /pmc/articles/PMC6231377/ /pubmed/30510965 http://dx.doi.org/10.1155/2018/5804230 Text en Copyright © 2018 Marcella Tazzari et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Tazzari, Marcella Brich, Silvia Tuccitto, Alessandra Bozzi, Fabio Beretta, Valeria Spagnuolo, Rosalin D. Negri, Tiziana Stacchiotti, Silvia Deraco, Marcello Baratti, Dario Camisaschi, Chiara Villa, Antonello Vergani, Barbara Rivoltini, Licia Pilotti, Silvana Castelli, Chiara Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types |
title | Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types |
title_full | Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types |
title_fullStr | Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types |
title_full_unstemmed | Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types |
title_short | Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types |
title_sort | complex immune contextures characterise malignant peritoneal mesothelioma: loss of adaptive immunological signature in the more aggressive histological types |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231377/ https://www.ncbi.nlm.nih.gov/pubmed/30510965 http://dx.doi.org/10.1155/2018/5804230 |
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