Pan-tumor spatial transcriptomics reveals conserved properties of tumor organization.

Tumor microenvironments (TMEs) are compositionally and functionally heterogeneous, making it challenging to discover organizing structural principles. Through a study of 262 solid tumors profiled by spatial transcriptomics, we identify a conserved architecture where TMEs are partitioned into discrete, hierarchically organized multicellular sub-regions, which we term "spatial groups" (SGs). As indicated by orthogonal spatial measurements and expert pathologist review, SGs associate with recognizable biological domains spanning global tissue context to local cellular neighborhoods. Comparing tumors through SGs reveals a pan-tumor classification where the dominant axis of variation is spatial heterogeneity of immune biology. In an independent, retrospective cohort of non-small cell lung cancer patients treated with immune checkpoint blockade (ICB; n = 16), pan-tumor spatial biology classification distinguishes clinical response and captures structural and biological hallmarks associated with ICB sensitivity. Together, these findings suggest that SGs may be important organizing domains of the TME that relate spatial structure, biological function, and response to therapy.