{Reference Type}: Journal Article
{Title}: Epithelioid Pleural Mesothelioma Is Characterized by Tertiary Lymphoid Structures in Long Survivors: Results from the MATCH Study.
{Author}: Mannarino L;Paracchini L;Pezzuto F;Olteanu GE;Moracci L;Vedovelli L;De Simone I;Bosetti C;Lupi M;Amodeo R;Inglesi A;Callari M;Penpa S;Libener R;Delfanti S;De Angelis A;Muzio A;Zucali PA;Allavena P;Ceresoli GL;Marchini S;Calabrese F;D'Incalci M;Grosso F;
{Journal}: Int J Mol Sci
{Volume}: 23
{Issue}: 10
{Year}: May 2022 21
{Factor}: 6.208
{DOI}: 10.3390/ijms23105786
{Abstract}: 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.