Potential diagnostic and prognostic role of micro-environment in malignant pleural mesothelioma
| Autor: | Federico Bussolino, Monica Pradotto, Francesca Napoli, Paolo Bironzo, Lorena Costardi, Giorgio V. Scagliotti, Preeta Ananthanarayanan, Carlotta F. Cartia, Luisella Righi, Massimo Di Maio, Valentina Comunanza, Joanna Kopecka, Mauro Papotti, Iris Chiara Salaroglio, Erika Passone, Chiara Riganti, Matteo Gagliasso, Francesco Ardissone, Enrico Ruffini, Fabrizio Tabbò, Silvia Novello, Francesca Maletta, Vladan Milosevic |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Mesothelioma 0301 basic medicine Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Lung Neoplasms Pleural effusion T cell Lymphocyte Malignant pleural mesothelioma Tumor-infiltrating lymphocytes T-regulatory cells 03 medical and health sciences 0302 clinical medicine Immune system Biopsy Tumor Microenvironment medicine Humans medicine.diagnostic_test business.industry Mesothelioma Malignant Prognosis medicine.disease 030104 developmental biology medicine.anatomical_structure Oncology Tumor progression Immune checkpoints Myeloid-derived suppressor cells 030220 oncology & carcinogenesis Myeloid-derived Suppressor Cell Female business |
| Popis: | Introduction A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified. Methods We enrolled 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsy samples used for the pathologic diagnosis and the immune phenotype analyses were blindly investigated by multiparametric flow cytometry. The results were analyzed using the Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune phenotype data with patients’ outcome. Results The cutoffs of intratumor T-regulatory (>1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and 4.2%, respectively), CD4 molecule–positive (CD4+) programmed death 1–positive (PD-1+) (>5.2%) and CD8+PD-1+ (6.4%) cells, CD4+ lymphocyte activating 3–positive (LAG-3+) (>2.8% ) and CD8+LAG-3+ (>2.8%) cells, CD4+ T cell immunoglobulin and mucin domain 3–positive (TIM-3+) (>2.5%), and CD8+TIM-3+ (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intratumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes. The immune phenotype of pleural fluid cells had no prognostic significance. By contrast, the intratumor T-regulatory and MDSC levels significantly correlated with progression-free and overall survival, the PD-1+/LAG-3+/TIM-3+ CD4+ tumor-infiltrating lymphocytes correlated with overall survival. Conclusions A clear immune signature of pleural fluids and tissues of MPM patients may contribute to better predict patients’ outcome. |
| Databáze: | OpenAIRE |
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