Tumor microenvironments (TMEs) influence cancer progression but are complex and often differ between patients. Considering that microenvironment variations may reveal rules governing intratumoral cellular programs and disease outcome, we focused on tumor-to-tumor variation to examine 52 head and neck squamous cell carcinomas. We found that macrophage polarity—defined by
CXCL9
and
SPP1
(CS) expression but not by conventional M1 and M2 markers—had a noticeably strong prognostic association. CS macrophage polarity also identified a highly coordinated network of either pro- or antitumor variables, which involved each tumor-associated cell type and was spatially organized. We extended these findings to other cancer indications. Overall, these results suggest that, despite their complexity, TMEs coordinate coherent responses that control human cancers and for which CS macrophage polarity is a relevant yet simple variable.
Highlights d Xenografted HNSCC comprises multiple unevenly propagating clones d Postsurgical recurrences reproducibly show a substitution of dominating clones d Clones enriched in recurrences are initially sparse in primary tumors d Clones enriched in recurrences feature distinct phenotypic and genetic traits
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