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

• Published in: Nature 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
• Language: English
• Published: London Nature Publishing Group UK 18.08.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/51; 631/250/2520; 631/250/580; 692/308/575; 692/4020/1503/1828/1829; 692/53/2423; Biomarkers; Cancer; CD4 antigen; CD8 antigen; Density; Dimensional analysis; Foxp3 protein; Gastric cancer; Humanities and Social Sciences; Immune response; Immune system; Immunohistochemistry; Immunotherapy; Lymphocytes; Lymphocytes T; Microenvironments; multidisciplinary; Multiplexing; Patients; PD-1 protein; PD-L1 protein; Science; Science (multidisciplinary); Tumor microenvironment; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-32570-z

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.