High-Dimensional Spectral Cytometry Reveals Therapeutically Relevant Immune Subtypes in Gastric Cancer
bioRxiv (Cold Spring Harbor Laboratory)(2023)
摘要
Identification of locally advanced gastric cancer (GC) patients who might potentially benefit from immune-based strategies is limited by both the poor predictive quality of existing biomarkers, including molecular subtypes, tumor mutational burden, and PD-L1 expression, as well as inadequate understanding of the gastric cancer immune microenvironment. Here, we leveraged high-dimensional spectral cytometry to re-classify locally advanced gastric tumors based on immune composition. The gastric cancer microenvironment was comprised of a diverse immune infiltrate including high proportions of plasmablasts, macrophages, and myeloid-derived suppressor cells. Computational cell typing and sample clustering based on tiered broad immune and T-cell focused phenotyping identified three distinct immune subtypes. The most immunogenic subtype exhibited high proportions of activated CD4+ T-cells and plasmablasts and included tumors that would have been classified as non-immunogenic based on prior classifications. Analysis of gastric cancer patients treated with immune checkpoint blockade indicates that patients who responded to immunotherapy had a pre-treatment tumor composition that corresponded to higher immune scores from our analysis. This work establishes a novel immunological classification of gastric cancer including identification of patients and immune networks likely to benefit from immune-based therapies.
### Competing Interest Statement
VES has received speaking honoraria from Merck Pharmaceuticals. SAV is an advisor for Immunai and has been a consultant for Koch Disruptive Technologies. No other authors have relationships with outside entities to disclose.
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关键词
gastric cancer,therapeutically relevant immune subtypes,high-dimensional
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