CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers

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…

• NS
  National Science Foundation
• BS
  Bristol-Myers Squibb
• A
  AstraZeneca
• S
  Sanofi
• LI
  Ludwig Institute for Cancer Research
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  Awards: P5R5PM_203164, P400PM_183852
• SD
  Studienstiftung des Deutschen Volkes
• FI
  Fondation ISREC
• NI
  National Institutes of Health

  Awards: P01-CA240239, R01-CA218579
• G
  Genentech
• P
  Pharmacyclics