CD70 and PD-L1 (CD274) co-expression predicts poor clinical outcomes in patients with pleural mesothelioma.
CD70 and PD-L1 (CD274) co-expression predicts poor clinical outcomes in patients with pleural mesothelioma.
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DOI：
10.1002/cjp2.310
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发表时间：
2023-05
影响因子：
4.1
通讯作者：
Takahashi, Satoru
中科院分区：
文献类型：
--
作者：
Inaguma, Shingo;Ueki, Akane;Lasota, Jerzy;Komura, Masayuki;Sheema, Asraful Nahar;Czapiewski, Piotr;Langfort, Renata;Rys, Janusz;Szpor, Joanna;Waloszczyk, Piotr;Okon, Krzysztof;Biernat, Wojciech;Schrump, David S.;Hassan, Raffit;Miettinen, Markku;Takahashi, Satoru
关键词：
弥漫性胸膜间皮瘤（PM）是一种高度侵袭性的肿瘤，通常与短生存期有关。最近，一线免疫检查点抑制剂在不可切除的PM患者中的有效性被报道。CD70-CD27信号通过核因子κB （NF - κB）途径在促进T细胞扩增和分化中发挥协同刺激作用。相反，PD‐L1 (CD274) -PD‐1 （PDCD1）通路在正常情况下对免疫应答的调节至关重要。然而，CD70和PD‐L1的异常表达对CD70 - cd27和PD‐L1 - PD‐1通路的病理激活参与了肿瘤细胞的免疫逃避。在这项研究中，171例特征明确的pm包括上皮样（n = 144）、双相（n = 15）和肉瘤样（n = 12）组织型，采用免疫组织化学方法评估CD70、PD‐L1和免疫细胞标记（如CD3、CD4、CD8、CD56、PD‐1、FOXP3、CD68和CD163）。8%（14/171）的间皮瘤在肿瘤细胞膜上同时表达CD70和PD‐L1。共表达CD70和PD‐L1的pm在其微环境中含有大量的CD8+ (p = 0.0016)、FOXP3+ (p = 0.00075)和CD163+ (p = 0.0011)免疫细胞。在PM共表达CD70和PD‐L1的患者队列中，总生存率显著降低（p < 0.0001）。体外实验表明，PD‐L1和CD70可增强PM细胞的运动性和侵袭性。相反，PD‐L1抑制了PM细胞的增殖。PD‐L1增强间充质表型，如N‐钙粘蛋白上调。总的来说，这些发现表明CD70和PD‐L1都增强了PM的恶性表型，并减弱了抗肿瘤免疫反应。根据我们的观察，针对这些信号通路的联合治疗可能对PM患者有用。
Diffuse pleural mesothelioma (PM) is a highly aggressive tumour typically associated with short survival. Recently, the effectiveness of first‐line immune checkpoint inhibitors in patients with unresectable PM was reported. CD70–CD27 signalling plays a co‐stimulatory role in promoting T cell expansion and differentiation through the nuclear factor κB (NF‐κB) pathway. Conversely, the PD‐L1 (CD274)–PD‐1 (PDCD1) pathway is crucial for the modulation of immune responses in normal conditions. Nevertheless, pathological activation of both the CD70–CD27 and PD‐L1–PD‐1 pathways by aberrantly expressed CD70 and PD‐L1 participates in the immune evasion of tumour cells. In this study, 171 well‐characterised PMs including epithelioid (n = 144), biphasic (n = 15), and sarcomatoid (n = 12) histotypes were evaluated immunohistochemically for CD70, PD‐L1, and immune cell markers such as CD3, CD4, CD8, CD56, PD‐1, FOXP3, CD68, and CD163. Eight percent (14/171) of mesotheliomas simultaneously expressed CD70 and PD‐L1 on the tumour cell membrane. PMs co‐expressing CD70 and PD‐L1 contained significantly higher numbers of CD8+ (p = 0.0016), FOXP3+ (p = 0.00075), and CD163+ (p = 0.0011) immune cells within their microenvironments. Overall survival was significantly decreased in the cohort of patients with PM co‐expressing CD70 and PD‐L1 (p < 0.0001). In vitro experiments revealed that PD‐L1 and CD70 additively enhanced the motility and invasiveness of PM cells. In contrast, PM cell proliferation was suppressed by PD‐L1. PD‐L1 enhanced mesenchymal phenotypes such as N‐cadherin up‐regulation. Collectively, these findings suggest that CD70 and PD‐L1 both enhance the malignant phenotypes of PM and diminish anti‐tumour immune responses. Based on our observations, combination therapy targeting these signalling pathways might be useful in patients with PM.
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DOI：
10.1002/path.5361
发表时间：
2020-02
期刊：
The Journal of pathology
影响因子：
--
作者：
Inaguma S;Lasota J;Czapiewski P;Langfort R;Rys J;Szpor J;Waloszczyk P;Okoń K;Biernat W;Schrump DS;Hassan R;Kasai K;Miettinen M;Ikeda H
通讯作者：
Ikeda H
对医疗统计信息的自由使用的易于使用的软件“ EZR”的调查。
影响因子：
4.8
作者：
Kanda Y
通讯作者：
Kanda Y
影响因子：
2.6
作者：
Jak, Margot;Mous, Rogier;Van Oers, Marinus H. J.
通讯作者：
Van Oers, Marinus H. J.
影响因子：
4.8
作者：
Diegmann, Julia;Junker, Kerstin;von Eggeling, Ferdinand
通讯作者：
von Eggeling, Ferdinand
影响因子：
10.9
作者：
Harber J;Kamata T;Pritchard C;Fennell D
通讯作者：
Fennell D