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

作者：Yang Chen, Keren Jia, Yu Sun, Cheng Zhang, Yilin Li, Li Zhang, Zifan Chen, Jiangdong Zhang, Yajie Hu, Jiajia Yuan, Xingwang Zhao, Yanyan Li, Jifang Gong, Bin Dong, Xiaotian Zhang, Jian Li, Lin Shen · 发表于：Nature Communications · 年份：2022 · DOI：10.1038/s41467-022-32570-z · 被引用次数：208 · 研究领域：Cancer Immunotherapy and Biomarkers、Pancreatic and Hepatic Oncology Research、Immune cells in cancer

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 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.