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

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. 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.

Automated summary

This paper introduces a multiplexed immunohistochemistry method to predict potential treatment response in gastric cancer patients by considering the proximity of tumor infiltrating immune cells (TIICs). It is found that a single biomarker is not sufficient to identify patients who would benefit from anti-PD-1/PD-L1 therapy due to the complexity of the tumor microenvironment. By establishing a multi-dimensional TIIC signature, the response to immunotherapy and patient survival can be predicted.