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

Article Article scientifique Article CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers eng 2023-08-03 2023-08-04 author Bill Ruben 0000-0002-4674-2531 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.,AGORA Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Leman, Lausanne, Switzerland.,Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.,Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 974134 author Wirapati Pratyaksha 0000-0002-0327-4686 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.,AGORA Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Leman, Lausanne, Switzerland. 982767 author Messemaker Marius 0000-0002-7179-0594 Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.,Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands. author Roh Whijae 0000-0002-7395-9939 Broad Institute of Harvard and MIT, Cambridge, MA, USA. author Zitti Béatrice 0000-0003-4610-7535 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.,AGORA Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Leman, Lausanne, Switzerland. 973448 Département de pathologie et immunologie (PATIM) author Duval Florent 0000-0002-3652-184X Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.,AGORA Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Leman, Lausanne, Switzerland. 968529 Département de pathologie et immunologie (PATIM) author Kiss Mate 0000-0002-5649-0382 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.,AGORA Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Leman, Lausanne, Switzerland. 950431 Département de pathologie et immunologie (PATIM) author Park Jong Chul 0000-0002-1052-0734 Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.,Massachusetts General Hospital Cancer Center, Charlestown, MA, USA. author Saal Talia M 0000-0002-5472-2143 Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA. author Hoelzl Jan 0000-0002-6411-7422 Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.,Department of Medical Oncology, Heidelberg University Hospital, Heidelberg, Germany. author Tarussio David Swiss Cancer Center Leman, Lausanne, Switzerland.,Department of Oncology, Center for Experimental Therapeutics, Lausanne University Hospital (CHUV), Lausanne, Switzerland.,Ludwig Institute for Cancer Research, Lausanne, Switzerland. author Benedetti Fabrizio 0000-0002-9959-9142 Department of Oncology, Center for Experimental Therapeutics, Lausanne University Hospital (CHUV), Lausanne, Switzerland.,Ludwig Institute for Cancer Research, Lausanne, Switzerland. author Tissot Stéphanie 0000-0003-3080-4598 Swiss Cancer Center Leman, Lausanne, Switzerland.,Department of Oncology, Center for Experimental Therapeutics, Lausanne University Hospital (CHUV), Lausanne, Switzerland.,Ludwig Institute for Cancer Research, Lausanne, Switzerland. author Kandalaft Lana 0000-0002-1575-6674 AGORA Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Leman, Lausanne, Switzerland.,Department of Oncology, Center for Experimental Therapeutics, Lausanne University Hospital (CHUV), Lausanne, Switzerland.,Ludwig Institute for Cancer Research, Lausanne, Switzerland. author Varrone Marco 0000-0002-0538-3464 Swiss Cancer Center Leman, Lausanne, Switzerland.,Department of Computational Biology, University of Lausanne (UNIL), Lausanne, Switzerland.,Swiss Institute of Bioinformatics, Lausanne, Switzerland. author Ciriello Giovanni 0000-0003-2021-8683 AGORA Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Leman, Lausanne, Switzerland.,Department of Computational Biology, University of Lausanne (UNIL), Lausanne, Switzerland.,Swiss Institute of Bioinformatics, Lausanne, Switzerland. author Mckee Thomas Alexander 0000-0002-2147-3136 Division of Clinical Pathology, Diagnostic Department, Geneva University Hospitals (HUG), Geneva, Switzerland. 549937 Département de pathologie et immunologie (PATIM) author Monnier Yan Department of Otorhinolaryngology-Head and Neck Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland. 931300 Département des neurosciences cliniques (OTONO) author Mermod Maxime 0000-0001-5330-3097 Department of Otorhinolaryngology-Head and Neck Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland. 403327 author Blaum Emily M 0000-0002-8656-8216 Broad Institute of Harvard and MIT, Cambridge, MA, USA.,Massachusetts General Hospital Cancer Center, Charlestown, MA, USA. author Gushterova Irena 0000-0002-8405-6348 Broad Institute of Harvard and MIT, Cambridge, MA, USA.,Massachusetts General Hospital Cancer Center, Charlestown, MA, USA. author Gonye Anna L K 0000-0003-0034-1756 Broad Institute of Harvard and MIT, Cambridge, MA, USA.,Massachusetts General Hospital Cancer Center, Charlestown, MA, USA. author Hacohen Nir 0000-0002-2349-2656 Broad Institute of Harvard and MIT, Cambridge, MA, USA.,Massachusetts General Hospital Cancer Center, Charlestown, MA, USA. author Getz Gad 0000-0002-0936-0753 Broad Institute of Harvard and MIT, Cambridge, MA, USA.,Massachusetts General Hospital Cancer Center, Charlestown, MA, USA.,Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. author Mempel Thorsten R 0000-0001-8635-5424 Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.,Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA. author Klein Allon M 0000-0001-8913-7879 Department of Systems Biology, Harvard Medical School, Boston, MA, USA. author Weissleder Ralph 0000-0003-0828-4143 Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.,Department of Systems Biology, Harvard Medical School, Boston, MA, USA.,Department of Radiology, Massachusetts General Hospital, Boston, MA, USA. author Faquin William C 0000-0002-9043-7171 Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.,Department of Otolaryngology Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA. author Sadow Peter M 0000-0003-1036-6367 Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.,Department of Otolaryngology Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA. author Lin Derrick 0009-0000-5022-3438 Department of Otolaryngology Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA. author Pai Sara I Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.,Broad Institute of Harvard and MIT, Cambridge, MA, USA.,Massachusetts General Hospital Cancer Center, Charlestown, MA, USA.,Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. author Sade-Feldman Moshe 0000-0002-0022-0287 Broad Institute of Harvard and MIT, Cambridge, MA, USA.,Massachusetts General Hospital Cancer Center, Charlestown, MA, USA. author Pittet Mikaël 0000-0002-2060-4691 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.,AGORA Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Leman, Lausanne, Switzerland.,Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.,Ludwig Institute for Cancer Research, Lausanne, Switzerland.,Department of Oncology, Geneva University Hospitals (HUG), Geneva, Switzerland. 917678 Département de pathologie et immunologie (PATIM) 515-524 10.1126/science.ade2292 37535729 0036-8075 https://www.science.org/doi/10.1126/science.ade2292 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<i>CXCL9</i>and<i>SPP1</i>(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. Humans Macrophages / metabolism Squamous Cell Carcinoma of Head and Neck Prognosis Head and Neck Neoplasms / metabolism Tumor Microenvironment Chemokine CXCL9 / metabolism Osteopontin / metabolism Dewey 616.8 Dewey 616.07 Dewey 616 Swiss National Science Foundation Targeting the tumor endothelium to sensitize lung cancer to immune checkpoint inhibition 183852 CH Careers Swiss National Science Foundation Tumor-infiltrating DC3s in the perivascular space - relevance for cancer immunity? 203164 CH Careers 137 Département de pathologie et immunologie 21F 61 Département des neurosciences cliniques 226 56 Département de médecine 221 false 1336 Comprendre et manipuler le système immunitaire pour lutter contre le cancer 1024 476 Lymphomes MALT et réplication virale 807 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE234933 Science 381 6657 bdc86333-09b7-471d-b443-b7f25d4f99f8 Article (Published version) Restricted clx.pdf 3232829 application/pdf 1c8a6b6ec8058e42e725d67240843e9f36ff11a452d32c31b8659f27054031cc 251942f9-c9d0-4613-85b4-cf3a6cc5ed7a Supplemental data Restricted science.ade2292_mdar_reproducibilit.pdf 160187 application/pdf b3708e90455d72cbf6ab7c08e6cc3afbac3de9fe8734b2c7ded84ebbd0379162 e547697b-2b8a-4248-845f-b396a91de7ec Supplemental data Restricted science.ade2292_table_s1.csv 3190 text/csv 07b67dccf3746b209bd8795a42a6510c100ed5f2f81721998bd935afc889b62c f7f58f1e-2183-464e-89ae-861f00a09449 Supplemental data Restricted science.ade2292_table_s2.csv 25476 text/csv bfc79dee7f96d3a654486f4b8c31cba32a76711e8558a8aeb47f4dbf2eb4bd82 c1166660-5907-421f-bda0-799a3045ba9d Supplemental data Restricted science.ade2292_table_s3.csv 1954 text/csv 565f1be7133be7bd0f4640b6a6ce26bc14b252670547602733dd822f9a373f06 8b1dbe57-f236-4037-b62d-a11c156788e5 Supplemental data Restricted science.ade2292_table_s4.csv 21926 text/csv f0464adf5c6ab3a0e3d0e786ceefdefedbf23656898dcf0078a565f60fe9c1f8 73159eb2-dc1f-493d-9895-2b7ca670d5a9 Supplemental data Restricted science.ade2292_table_s5.csv 207443 text/csv 229cf497649e248a1da981af5f574d908f57bb8c36e180a37a626c43e03037b4 b8c41cc9-fc30-44be-bad3-0827630f5983 Supplemental data Restricted science.ade2292_table_s6.xlsx 41670 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 353e02907fa258eb39a9311ed8fdda85ef13b2deebe35f7a49513d08e9009fef 49189e55-d789-42ac-9405-f4f6e052b1ea Supplemental data Restricted science.ade2292_sm.pdf 18789904 application/pdf d7538a0c4b787cb67cd083c938fabbf0acd5a63fbcfec5262b2c0d64de66acbd restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques Faculté de médecine / Section de médecine clinique / Département de médecine

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