Een pan-kankeranalyse van het transcriptomische landschap van de tumor micro-omgeving

Pan-cancer single-cell atlases explore heterogeneity of cell types residing within the tumor-microenvironment (TME). So far, atlases focused on individual cell types, failing to capture the full complexity of the TME. Here, we present a single-cell atlas that simultaneously considers heterogeneity in 5 cell types, collected from 230 treatment-naïve samples across 9 cancer types. We identify 70 pan-cancer single-cell subtypes, investigate their patterns of co-occurrence and show enrichment of specific subtypes in certain TMEs, e.g. immune-reactive versus -suppressive TME. We observe 2 TME hubs of strongly co-occurring subtypes: one hub resembling tertiary lymphoid structures (TLSs), another consisting of immune-reactive PD1+/PD-L1+ immune-regulatory T- and B-cells, dendritic cells and inflammatory macrophages. Subtypes belonging to each hub are also spatially co-localized, while their abundance associates with prediction to early and long-term checkpoint immunotherapy response. We publicly share our atlas as a Shiny app, allowing others to explore TME heterogeneity in different biological contexts.