Epithelioid Pleural Mesothelioma Is Characterized by Tertiary Lymphoid Structures in Long Survivors: Results from the MATCH Study

International Journal of Molecular Sciences 2022 May 21 [Link]

Laura Mannarino, Lara Paracchini, Federica Pezzuto, Gheorghe Emilian Olteanu, Laura Moracci, Luca Vedovelli, Irene De Simone, Cristina Bosetti, Monica Lupi, Rosy Amodeo, Alessia Inglesi, Maurizio Callari, Serena Penpa, Roberta Libener, Sara Delfanti, Antonina De Angelis, Alberto Muzio, Paolo Andrea Zucali, Paola Allavena, Giovanni Luca Ceresoli, Sergio Marchini, Fiorella Calabrese, Maurizio D’Incalci, Federica Grosso


Pleural mesothelioma (PM) is an aggressive tumor with few therapeutic options. Although patients with epithelioid PM (ePM) survive longer than non-epithelioid PM (non-ePM), heterogeneity of tumor response in ePM is observed. The role of the tumor immune microenvironment (TIME) in the development and progression of PM is currently considered a promising biomarker. A few studies have used high-throughput technologies correlated with TIME evaluation and morphologic and clinical data. This study aimed to identify different morphological, immunohistochemical, and transcriptional profiles that could potentially predict the outcome. A retrospective multicenter cohort of 129 chemonaive PM patients was recruited. Tissue slides were reviewed by dedicated pathologists for histotype classification and immunophenotype of tumor-infiltrating lymphocytes (TILs) and lymphoid aggregates or tertiary lymphoid structures (TLS). ePM (n = 99) survivors were further classified into long (>36 months) or short (<12 months) survivors. RNAseq was performed on a subset of 69 samples. Distinct transcriptional profiling in long and short ePM survivors was found. An inflammatory background with a higher number of B lymphocytes and a prevalence of TLS formations were detected in long compared to short ePM survivors. These results suggest that B cell infiltration could be important in modulating disease aggressiveness, opening a pathway for novel immunotherapeutic approaches.