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透明细胞肾细胞癌免疫细胞浸润景观,以辅助免疫治疗。

Landscape of immune cell infiltration in clear cell renal cell carcinoma to aid immunotherapy.

机构信息

Frontiers Science Center for Flexible Electronics, Institute of Flexible Electronics, MIIT Key Laboratory of Flexible Electronics, Northwestern Polytechnical University, Xi'an, China.

Research and Development Institute of Northwestern Polytechnical University in Shenzhen, Northwestern Polytechnical University, Xi'an, China.

出版信息

Cancer Sci. 2021 Jun;112(6):2126-2139. doi: 10.1111/cas.14887. Epub 2021 Apr 7.

DOI:10.1111/cas.14887
PMID:33735492
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8177771/
Abstract

The tumor microenvironment, comprised of tumor cells and tumor-infiltrating immune cells, is closely associated with the clinical outcome of clear cell renal cell carcinoma (ccRCC) patients. However, the landscape of immune infiltration in ccRCC has not been fully elucidated. Herein, we applied multiple computational methods and various datasets to reveal the immune infiltrative landscape of ccRCC patients. The tumor immune infiltration (TII) levels of 525 ccRCC patients using a single-sample gene were examined and further categorized into immune infiltration subgroups. The TII score was characterized by distinct clinical traits and showed a significant divergence based on gender, grade, and stage. A high TII score was associated with the ERBB signaling pathway, the TGF-β signaling pathway, and the MTOR signaling pathway, as well as a better prognosis. Furthermore, patients with high TII scores exhibited greater sensitivity to pazopanib. The low TII score was characterized by a high immune infiltration level of CD8 T cells, T follicular helper cells, and regulatory T cells (Tregs). Moreover, the immune check point genes, including CTLA-4, LAG3, PD-1, and IDO1, presented a high expression level in the low TII score group. Patients in the high TII score group demonstrated significant therapeutic advantages and clinical benefits. The findings in this study have the potential to assist in the strategic design of immunotherapeutic treatments for ccRCC.

摘要

肿瘤微环境由肿瘤细胞和肿瘤浸润免疫细胞组成,与透明细胞肾细胞癌(ccRCC)患者的临床结局密切相关。然而,ccRCC 中的免疫浸润情况尚未完全阐明。在此,我们应用多种计算方法和多个数据集来揭示 ccRCC 患者的免疫浸润景观。使用单个样本基因检查了 525 名 ccRCC 患者的肿瘤免疫浸润(TII)水平,并进一步分为免疫浸润亚组。TII 评分具有明显的临床特征,并且根据性别、分级和分期存在显著差异。高 TII 评分与 ERBB 信号通路、TGF-β 信号通路和 MTOR 信号通路相关,并具有较好的预后。此外,高 TII 评分的患者对帕唑帕尼更敏感。低 TII 评分的特点是 CD8 T 细胞、滤泡辅助 T 细胞和调节性 T 细胞(Tregs)的高水平免疫浸润。此外,免疫检查点基因,包括 CTLA-4、LAG3、PD-1 和 IDO1,在低 TII 评分组中呈现高表达水平。高 TII 评分组的患者表现出显著的治疗优势和临床获益。本研究的结果有可能有助于为 ccRCC 的免疫治疗策略设计提供参考。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29d7/8177771/946ffdd98742/CAS-112-2126-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29d7/8177771/aef681ec88e1/CAS-112-2126-g012.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29d7/8177771/f9f6fe5b7675/CAS-112-2126-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29d7/8177771/82342935b623/CAS-112-2126-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29d7/8177771/3b84723a06e6/CAS-112-2126-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29d7/8177771/06596c1ee67d/CAS-112-2126-g011.jpg
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