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通过肿瘤免疫微环境的多维分析预测胃癌对免疫治疗的反应。

Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment.

机构信息

Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.

Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.

出版信息

Nat Commun. 2022 Aug 18;13(1):4851. doi: 10.1038/s41467-022-32570-z.

DOI:10.1038/s41467-022-32570-z
PMID:35982052
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9388563/
Abstract

A single biomarker is not adequate to identify patients with gastric cancer (GC) who have the potential to benefit from anti-PD-1/PD-L1 therapy, presumably owing to the complexity of the tumour microenvironment. The predictive value of tumour-infiltrating immune cells (TIICs) has not been definitively established with regard to their density and spatial organisation. Here, multiplex immunohistochemistry is used to quantify in situ biomarkers at sub-cellular resolution in 80 patients with GC. To predict the response to immunotherapy, we establish a multi-dimensional TIIC signature by considering the density of CD4FoxP3PD-L1, CD8PD-1LAG3, and CD68STING cells and the spatial organisation of CD8PD-1LAG3 T cells. The TIIC signature enables prediction of the response of patients with GC to anti-PD-1/PD-L1 immunotherapy and patient survival. Our findings demonstrate that a multi-dimensional TIIC signature may be relevant for the selection of patients who could benefit the most from anti-PD-1/PD-L1 immunotherapy.

摘要

单一生物标志物不足以识别有可能从抗 PD-1/PD-L1 治疗中获益的胃癌 (GC) 患者,这可能归因于肿瘤微环境的复杂性。肿瘤浸润免疫细胞 (TIIC) 的密度和空间组织与它们的预测价值尚未得到明确确定。在这里,使用多重免疫组织化学在 80 名 GC 患者中以亚细胞分辨率定量原位生物标志物。为了预测免疫治疗的反应,我们通过考虑 CD4FoxP3PD-L1、CD8PD-1LAG3 和 CD68STING 细胞的密度以及 CD8PD-1LAG3 T 细胞的空间组织,建立了一个多维 TIIC 特征。TIIC 特征可预测 GC 患者对抗 PD-1/PD-L1 免疫治疗的反应和患者的生存情况。我们的研究结果表明,多维 TIIC 特征可能与选择最能从抗 PD-1/PD-L1 免疫治疗中获益的患者有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a157/9388563/98ffee07e3f5/41467_2022_32570_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a157/9388563/22cd568e8484/41467_2022_32570_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a157/9388563/fcc6a78010ff/41467_2022_32570_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a157/9388563/98ffee07e3f5/41467_2022_32570_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a157/9388563/22cd568e8484/41467_2022_32570_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a157/9388563/00789587129c/41467_2022_32570_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a157/9388563/d6eaf249d680/41467_2022_32570_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a157/9388563/fcc6a78010ff/41467_2022_32570_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a157/9388563/98ffee07e3f5/41467_2022_32570_Fig5_HTML.jpg

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