Characterization of the immune microenvironment in malignant pleural mesothelioma reveals prognostic subgroups of patients

Fusco, Nicola; Vaira, Valentina; Righi, I.; Sajjadi, Elham; Venetis, Konstantinos; Lopez, Gianluca; Cattaneo, M.; Castellani, Massimo; Rosso, Lorenzo; Nosotti, Mario; Clerici, Mario; Ferrero, Stefano

doi:10.1016/j.lungcan.2020.09.026

Cited by 36 publications

(40 citation statements)

References 34 publications

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“…In another IHC analysis of 88 MPM tumors, PD-L1 was expressed regardless of the MPM histologic subtype, but both PD-L1 positive tumors and sarcomatoid MPM showed an increase of stromal CD4+ and CD19+ lymphocytes. In contrast, epithelioid tumors were associated with a higher proportion of CD8+ cells (24).…”

Section: The Immunosuppressive Phenotypementioning

confidence: 82%

“…In this study, CD4+ cells correlated with improved prognosis (HR 0.48 [0.24-0.96] p=0.036), while CD8 infiltration correlated with poor prognosis (for low CD8, HR 0.44 [0.27-0.72] p=0.0012). Consequently, a high stromal CD4/CD8 ratio was found to be an independent predictor of longer survival in a multivariate model accounting for histology and PD-L1 status (24). Moreover, associations between tumor infiltrating lymphocytes (TIL) and survival were observed to change in presence of systemic therapy.…”

Section: The Immunosuppressive Phenotypementioning

confidence: 93%

“…In addition to their effect on the TIL composition, the relative composition of the lymphoid infiltrate itself was found to be an independent predictor of outcomes. The balance between CD4 and CD8 T cells is key in this respect (24,25). Fusco and collaborators (24) analyzed 88 MPM tumors.…”

Section: The Immunosuppressive Phenotypementioning

confidence: 99%

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Immune Microenvironment and Genetics in Malignant Pleural Mesothelioma

2021

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Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with limited therapeutic options beyond surgery and cytotoxic chemotherapy. The success of immune checkpoint inhibition has been found to correlate with expression of immune-related genes such as CD274 (PD-L1) in lung and other solid cancers. However, only a small subset of MPM patients respond to checkpoint inhibition, and this response has been varied and unpredictable across several clinical trials. Recent advances in next-generation sequencing (NGS) technology have improved our understanding of the molecular features of MPM, also with respect to its genetic signature and how this impacts the immune microenvironment. This article will review current evidence surrounding the interplay between MPM genetics, including epigenetics and transcriptomics, and the immune response.

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Section: The Immunosuppressive Phenotypementioning

confidence: 82%

Section: The Immunosuppressive Phenotypementioning

confidence: 93%

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Immune Microenvironment and Genetics in Malignant Pleural Mesothelioma

2021

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“…Moreover, Fusco et al found an increased presence of stromal CD4+ T and CD19+ B lymphocytes with a positive correlation between each other, possibly indicating a positive feedback loop between these two lineages [ 92 ].…”

Section: The Tumor Immune Microenvironmentmentioning

confidence: 99%

Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma

Napoli

Listì

Zambelli

et al. 2021

Cancers

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Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13–15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients’ genetic predisposition and tumor genomic profile. The chronic inflammatory response to asbestos fibers leads to a unique tumor immune microenvironment (TIME) composed of a heterogeneous mixture of stromal, endothelial, and immune cells, and relative composition and interaction among them is suggested to bear prognostic and therapeutic implications. TIME in MPM is known to be constituted by immunosuppressive cells, such as type 2 tumor-associated macrophages and T regulatory lymphocytes, plus the expression of several immunosuppressive factors, such as tumor-associated PD-L1. Several studies in recent years have contributed to achieve a greater understanding of the pathogenetic mechanisms in tumor development and pathobiology of TIME, that opens the way to new therapeutic strategies. The study of TIME is fundamental in identifying appropriate prognostic and predictive tissue biomarkers. In the present review, we summarize the current knowledge about the pathological characterization of TIME in MPM.

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“…Finally, in malignant pleural mesotheliomas (MPMs), low CD4 POS and high CD8 POS sTILs are associated with poor patients' survival [78]. In MPMs PD-L1 CPS > 1, stromal CD8 HIGH seems to be a poor prognostic factor, while stromal CD4 POS peritumoural TILs correlate with a worse prognosis [78]. In these tumours, a high CD4 POS /CD8 POS ratio in the immune microenvironment is an independent prognostic factor for survival.…”

Section: Tumour-infiltrating Lymphocytes (Tils)mentioning

confidence: 99%

Biomarkers for precision immunotherapy in the metastatic setting: hope or reality?

Sajjadi¹,

Venetis²,

Scatena³

et al. 2020

ecancer

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Precision immunotherapy is a crucial approach to improve the efficacy of anti-cancer treatments, particularly in the metastatic setting. In this respect, accurate patient selection takes advantage of the multidimensional integration of patients' clinical information and tumourspecific biomarkers status. Among these biomarkers, programmed death-ligand 1, tumourinfiltrating lymphocytes, microsatellite instability, mismatch repair and tumour mutational burden have been widely investigated. However, novel tumour-specific biomarkers and testing methods will further improve patients' outcomes. Here, we discuss the currently available strategies for the implementation of a precision immunotherapy approach in the clinical management of metastatic solid tumours and highlight future perspectives.

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Characterization of the immune microenvironment in malignant pleural mesothelioma reveals prognostic subgroups of patients

Cited by 36 publications

References 34 publications

Immune Microenvironment and Genetics in Malignant Pleural Mesothelioma

Immune Microenvironment and Genetics in Malignant Pleural Mesothelioma

Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma

Biomarkers for precision immunotherapy in the metastatic setting: hope or reality?

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