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

Author:

Chen YangORCID,Jia KerenORCID,Sun YuORCID,Zhang ChengORCID,Li YilinORCID,Zhang LiORCID,Chen ZifanORCID,Zhang Jiangdong,Hu Yajie,Yuan JiajiaORCID,Zhao Xingwang,Li YanyanORCID,Gong Jifang,Dong BinORCID,Zhang Xiaotian,Li Jian,Shen LinORCID

Abstract

AbstractA 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+FoxP3PD-L1+, CD8+PD-1LAG3, 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.

Funder

Natural Science Foundation of Beijing Municipality

Innovation Fund for Outstanding Doctoral Candidates of Peking University Health Science Cente

National Natural Science Foundation of China

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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