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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.
摘要：
胸膜间皮瘤（PM）是一种侵袭性肿瘤，几乎没有治疗选择。尽管上皮样PM（ePM）患者比非上皮样PM（非ePM）患者存活时间更长，在ePM中观察到肿瘤反应的异质性。肿瘤免疫微环境（TIME）在PM的发生和发展中的作用目前被认为是有前途的生物标志物。一些研究使用了与TIME评估以及形态学和临床数据相关的高通量技术。本研究旨在鉴定不同的形态学,免疫组织化学，和可能预测结果的转录谱。招募了129名化疗患者的回顾性多中心队列。专门的病理学家对组织载玻片进行了审查，以了解肿瘤浸润淋巴细胞（TIL）和淋巴聚集体或三级淋巴结构（TLS）的组织型分类和免疫表型。ePM（n=99）幸存者进一步分为长（>36个月）或短（<12个月）幸存者。对69个样品的子集进行RNAseq。在长和短ePM幸存者中发现了不同的转录谱。与短ePM幸存者相比，长期检测到具有较高数量B淋巴细胞的炎症背景和TLS形成的患病率。这些结果表明，B细胞浸润在调节疾病侵袭性方面可能很重要，为新的免疫治疗方法开辟了一条途径。
