CCL11/CCR3-dependent eosinophilia alleviates malignant pleural effusions and improves prognosis

IF 6.8 1区 医学 Q1 ONCOLOGY NPJ Precision Oncology Pub Date : 2024-06-29 DOI:10.1038/s41698-024-00608-8
Min Zhang, Lixia Xia, Wenbei Peng, Guogang Xie, Fei Li, Chao Zhang, Madiha Zahra Syeda, Yue Hu, Fen Lan, Fugui Yan, Zhangchu Jin, Xufei Du, Yinling Han, Baihui Lv, Yuejue Wang, Miao Li, Xia Fei, Yun Zhao, Kaijun Chen, Yan Chen, Wen Li, Zhihua Chen, Qiong Zhou, Min Zhang, Songmin Ying, Huahao Shen
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Abstract

Malignant pleural effusion (MPE) is a common occurrence in advanced cancer and is often linked with a poor prognosis. Eosinophils were reported to involve in the development of MPE. However, the role of eosinophils in MPE remains unclear. To investigate this, we conducted studies using both human samples and mouse models. Increased eosinophil counts were observed in patients with MPE, indicating that the higher the number of eosinophils is, the lower the LENT score is. In our animal models, eosinophils were found to migrate to pleural cavity actively upon exposure to tumor cells. Intriguingly, we discovered that a deficiency in eosinophils exacerbated MPE, possibly due to their anti-tumor effects generated by modifying the microenvironment of MPE. Furthermore, our experiments explored the role of the C-C motif chemokine ligand 11 (CCL11) and its receptor C-C motif chemokine receptor 3 (CCR3) in MPE pathology. As a conclusion, our study underscores the protective potential of eosinophils against the development of MPE, and that an increase in eosinophils through adoptive transfer of eosinophils or increasing their numbers improved MPE.

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CCL11/CCR3 依赖性嗜酸性粒细胞减少可缓解恶性胸腔积液并改善预后。
恶性胸腔积液(MPE)是晚期癌症的常见病,通常与预后不良有关。据报道,嗜酸性粒细胞参与了恶性胸腔积液的形成。然而,嗜酸性粒细胞在 MPE 中的作用仍不清楚。为了探究这个问题,我们使用人体样本和小鼠模型进行了研究。在 MPE 患者中观察到嗜酸性粒细胞数量增加,这表明嗜酸性粒细胞数量越多,LENT 评分越低。在动物模型中,我们发现嗜酸性粒细胞在接触肿瘤细胞后会主动迁移到胸膜腔。有趣的是,我们发现嗜酸性粒细胞的缺乏会加重 MPE,这可能是由于嗜酸性粒细胞通过改变 MPE 的微环境产生了抗肿瘤作用。此外,我们的实验还探讨了 C-C motif 趋化因子配体 11(CCL11)及其受体 C-C motif 趋化因子受体 3(CCR3)在 MPE 病理学中的作用。总之,我们的研究强调了嗜酸性粒细胞对 MPE 发生的潜在保护作用,通过嗜酸性粒细胞的收养性转移或增加其数量来增加嗜酸性粒细胞可改善 MPE。
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来源期刊
CiteScore
9.90
自引率
1.30%
发文量
87
审稿时长
18 weeks
期刊介绍: Online-only and open access, npj Precision Oncology is an international, peer-reviewed journal dedicated to showcasing cutting-edge scientific research in all facets of precision oncology, spanning from fundamental science to translational applications and clinical medicine.
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