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

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 definitive...

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Published inNature communications Vol. 13; no. 1; pp. 4851 - 12
Main Authors Chen, Yang, Jia, Keren, Sun, Yu, Zhang, Cheng, Li, Yilin, Zhang, Li, Chen, Zifan, Zhang, Jiangdong, Hu, Yajie, Yuan, Jiajia, Zhao, Xingwang, Li, Yanyan, Gong, Jifang, Dong, Bin, Zhang, Xiaotian, Li, Jian, Shen, Lin
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 18.08.2022
Nature Publishing Group
Nature Portfolio
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ISSN2041-1723
2041-1723
DOI10.1038/s41467-022-32570-z

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Summary: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 CD4 + FoxP3 − PD-L1 + , CD8 + PD-1 − LAG3 − , and CD68 + STING + cells and the spatial organisation of CD8 + PD-1 + LAG3 − 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. Predictive methods for gastric cancer to try and differentiate between potential treatment response are required. Here the authors use a multiplexed immunohistochemistry method to propose the proximity of tumour infiltrating immune cells as an indicator of likely therapeutic response.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-32570-z