Characterization of Pleural Mesothelioma by Hierarchical Clustering Analyses Using Immune Cells within Tumor Microenvironment.

IF 3.5 4区医学 Q3 CELL BIOLOGY

Pathobiology Pub Date : 2024-01-01 Epub Date: 2024-03-25 DOI:10.1159/000538520

Shingo Inaguma, Chengbo Wang, Sunao Ito, Akane Ueki, Jerzy Lasota, Piotr Czapiewski, Renata Langfort, Janusz Rys, Joanna Szpor, Piotr Waloszczyk, Krzysztof Okoń, Wojciech Biernat, Shuji Takiguchi, David S Schrump, Markku Miettinen, Satoru Takahashi

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引用次数: 0

Abstract

Introduction: Over the past decade, classifications using immune cell infiltration have been applied to many types of tumors; however, mesotheliomas have been less frequently evaluated.

Methods: In this study, 60 well-characterized pleural mesotheliomas (PMs) were evaluated immunohistochemically for the characteristics of immune cells within tumor microenvironment (TME) using 10 immunohistochemical markers: CD3, CD4, CD8, CD56, CD68, CD163, FOXP3, CD27, PD-1, and TIM-3. For further characterization of PMs, hierarchical clustering analyses using these 10 markers were performed.

Results: Among the immune cell markers, CD3 (p < 0.0001), CD4 (p = 0.0016), CD8 (p = 0.00094), CD163+ (p = 0.042), and FOXP3+ (p = 0.025) were significantly associated with an unfavorable clinical outcome. Immune checkpoint receptor expressions on tumor-infiltrating lymphocytes such as PD-1 (p = 0.050), CD27 (p = 0.014), and TIM-3 (p = 0.0098) were also associated with unfavorable survival. Hierarchical clustering analyses identified three groups showing specific characteristics and significant associations with patient survival (p = 0.016): the highest number of immune cells (ICHigh); the lowest number of immune cells, especially CD8+ and CD163+ cells (ICLow); and intermediate number of immune cells (ICInt). ICHigh tumors showed significantly higher expression of PD-L1 (p = 0.00038). Cox proportional hazard model identified ICHigh [hazard ratio (HR) = 2.90] and ICInt (HR = 2.97) as potential risk factors compared with ICLow. Tumor CD47 (HR = 2.36), tumor CD70 (HR = 3.04), and tumor PD-L1 (HR = 3.21) expressions were also identified as potential risk factors for PM patients.

Conclusion: Our findings indicate immune checkpoint and/or immune cell-targeting therapies against CD70-CD27 and/or CD47-SIRPA axes may be applied for PM patients in combination with PD-L1-PD-1 targeting therapies in accordance with their tumor immune microenvironment characteristics.

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利用肿瘤微环境中的免疫细胞进行分层聚类分析，确定胸膜间皮瘤的特征。

简介：过去十年中，许多类型的肿瘤都采用了免疫细胞浸润分类法，但对间皮瘤的评估较少：在过去十年中，利用免疫细胞浸润进行的分类已被应用于多种类型的肿瘤；然而，对间皮瘤的评估却较少：本研究使用 10 种免疫组化标记 CD3、CD4、CD8、CD56、CD68、CD163、FOXP3、CD27、PD-1 和 TIM-3 对 60 例特征明确的胸膜间皮瘤（PMs）进行了免疫组化评估，以了解肿瘤微环境（TME）中免疫细胞的特征。为了进一步确定 PMs 的特征，研究人员使用这 10 个标记物进行了分层聚类分析：结果：在免疫细胞标记物中，CD3（P < 0.0001）、CD4（P = 0.0016）、CD8（P = 0.00094）、CD163+（P = 0.042）和FOXP3+（P = 0.025）与不利的临床结局显著相关。肿瘤浸润淋巴细胞上免疫检查点受体的表达，如PD-1（P = 0.050）、CD27（P = 0.014）和TIM-3（P = 0.0098），也与不利的生存率有关。分层聚类分析确定了三个显示特定特征并与患者生存显著相关（P = 0.011）的组别：免疫细胞数量最多（ICHigh）；免疫细胞数量最少，尤其是CD8+和CD163+细胞（ICLow）；免疫细胞数量居中（ICInt）。ICHigh肿瘤的PD-L1表达量明显更高（P = 0.00038）。Cox 比例危险模型发现，与 ICLow 相比，ICHigh [危险比 (HR) = 2.90] 和 ICInt（HR = 2.97）是潜在的危险因素。肿瘤CD47（HR = 2.36）、肿瘤CD70（HR = 3.04）和肿瘤PD-L1（HR = 3.21）的表达也被确定为PM患者的潜在危险因素：我们的研究结果表明，针对CD70-CD27和/或CD47-SIRPA轴的免疫检查点和/或免疫细胞靶向疗法可与PD-L1-PD-1靶向疗法相结合，根据肿瘤免疫微环境的特点应用于PM患者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathobiology 医学-病理学

CiteScore

8.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： ''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.