DOI: 10.1126/science.ade2292 ISSN: 0036-8075

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

Ruben Bill, Pratyaksha Wirapati, Marius Messemaker, Whijae Roh, Beatrice Zitti, Florent Duval, Máté Kiss, Jong Chul Park, Talia M. Saal, Jan Hoelzl, David Tarussio, Fabrizio Benedetti, Stéphanie Tissot, Lana Kandalaft, Marco Varrone, Giovanni Ciriello, Thomas A. McKee, Yan Monnier, Maxime Mermod, Emily M. Blaum, Irena Gushterova, Anna L. K. Gonye, Nir Hacohen, Gad Getz, Thorsten R. Mempel, Allon M. Klein, Ralph Weissleder, William C. Faquin, Peter M. Sadow, Derrick Lin, Sara I. Pai, Moshe Sade-Feldman, Mikael J. Pittet
  • Multidisciplinary

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.

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