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

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
Nature communications | 2022

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.

Pubmed ID: 35982052

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Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

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Sklearn (tool)

RRID:SCR_019053

Software Python package part of nonnegative matrix factorization NMF. Features various classification, regression and clustering algorithms including support vector machines, random forests, gradient boosting, k-means and DBSCAN, and is designed to interoperate with Python numerical and scientific libraries NumPy and SciPy.

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