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首页> 外文期刊>Journal of immunology research. >Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types
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Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types

机译：复杂的免疫语境表征恶性腹膜间皮瘤：在更具攻击性的组织学类型中的适应性免疫特征的丧失。

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Malignant peritoneal mesothelioma (MpM), arising in the setting of local inflammation, is a rare aggressive tumour with a poor prognosis and limited therapeutic options. The three major MpM histological variants, epithelioid (E-MpMs), biphasic, and sarcomatoid MpMs (S-MpMs), are characterised by an increased aggressiveness and enhanced levels of EZH2 expression. To investigate the MpM immune contexture along the spectrum of MpM histotypes, an extended in situ analysis was performed on a series of 14 cases. Tumour-infiltrating immune cells and their functionality were assessed by immunohistochemistry, immunofluorescence, qRT-PCR, and flow cytometry analysis. MpMs are featured by a complex immune landscape modulated along the spectrum of MpM variants. Tumour-infiltrating T cells and evidence for pre-existing antitumour immunity are mainly confined to E-MpMs. However, Th1-related immunological features are progressively impaired in the more aggressive forms of E-MpMs and completely lost in S-MpM. Concomitantly, E-MpMs show also signs of active immune suppression, such as the occurrence of Tregs and Bregs and the expression of the immune checkpoint inhibitory molecules PD1 and PDL1. This study enriches the rising rationale for immunotherapy in MpM and points to the E-MpMs as the most immune-sensitive MpM histotypes, but it also suggests that synergistic interventions aimed at modifying the tumour microenvironment (TME) should be considered to make immunotherapy beneficial for these patients.
机译：恶性腹膜间皮瘤（MpM）发生于局部炎症，是一种罕见的侵袭性肿瘤，预后差，治疗选择有限。 MpM的三种主要组织学变异是上皮样（E-MpMs），双相性和肉瘤样MpMs（S-MpMs），其特征是侵略性增强和EZH2表达水平提高。为了调查沿MpM组织型谱的MpM免疫情况，对一系列14例病例进行了扩展的原位分析。通过免疫组织化学，免疫荧光，qRT-PCR和流式细胞仪分析评估了浸润肿瘤的免疫细胞及其功能。 MpM的特征是沿着MpM变体的光谱进行调节的复杂免疫格局。肿瘤浸润性T细胞和已有抗肿瘤免疫力的证据主要限于E-MpMs。但是，Th1相关的免疫学特征在更具侵略性的E-MpM中逐渐受损，而在S-MpM中则完全消失。同时，E-MpMs还显示出主动免疫抑制的迹象，例如Treg和Breg的出现以及免疫检查点抑制分子PD1和PDL1的表达。这项研究丰富了MpM免疫疗法不断发展的理论基础，并指出E-MpMs是对免疫敏感性最强的MpM组织型，但同时也建议旨在改善肿瘤微环境（TME）的协同干预措施可使免疫治疗对MpM有益这些病人。

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