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

• 成果类型: Article
• 署名作者: Bill, Ruben; Wirapati, Pratyaksha; Messemaker, Marius; Roh, Whijae; Zitti, Beatrice; Duval, Florent; Kiss, Mate; Park, Jong Chul; Saal, Talia M.; Hoelzl, Jan; Tarussio, David; Benedetti, Fabrizio; Tissot, Stephanie; Kandalaft, Lana; Varrone, Marco; Ciriello, Giovanni; McKee, Thomas A.; Monnier, Yan; Mermod, Maxime; Blaum, Emily M.; Gushterova, Irena; Gonye, Anna L. K.; Hacohen, Nir; Getz, Gad; Mempel, Thorsten R.; Klein, Allon M.; Weissleder, Ralph; Faquin, William C.; Sadow, Peter M.; Lin, Derrick; Pai, Sara I.; Sade-Feldman, Moshe; Pittet, Mikael J.
• 署名单位: University of Geneva; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; University of Bern; University Hospital of Bern; Netherlands Cancer Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Ruprecht Karls University Heidelberg; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Ludwig Institute for Cancer Research; University of Lausanne; Swiss Institute of Bioinformatics; University of Geneva; University of Geneva; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts Eye & Ear Infirmary; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; University of Geneva
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11682
• DOI: 10.1126/science.ade2292
• 发表日期: 2023-08-04
• 页码: 515-524
• 关键词: tumor-associated macrophages; regularization paths; gene-expression; immune cells; survival; head; immunotherapy; lymphocytes; target; MODEL

摘要

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.