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

Author:

Bill Ruben12345ORCID,Wirapati Pratyaksha123ORCID,Messemaker Marius46ORCID,Roh Whijae7ORCID,Zitti Beatrice123ORCID,Duval Florent123ORCID,Kiss Máté123ORCID,Park Jong Chul89ORCID,Saal Talia M.4ORCID,Hoelzl Jan410ORCID,Tarussio David31112,Benedetti Fabrizio1112ORCID,Tissot Stéphanie31112ORCID,Kandalaft Lana231112ORCID,Varrone Marco31314ORCID,Ciriello Giovanni231314ORCID,McKee Thomas A.15ORCID,Monnier Yan16,Mermod Maxime16ORCID,Blaum Emily M.79ORCID,Gushterova Irena79ORCID,Gonye Anna L. K.79ORCID,Hacohen Nir79ORCID,Getz Gad7917ORCID,Mempel Thorsten R.418ORCID,Klein Allon M.19ORCID,Weissleder Ralph41920ORCID,Faquin William C.1721ORCID,Sadow Peter M.1721ORCID,Lin Derrick21ORCID,Pai Sara I.47922,Sade-Feldman Moshe79ORCID,Pittet Mikael J.123412ORCID

Affiliation:

1. Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.

2. AGORA Cancer Research Center, Lausanne, Switzerland.

3. Swiss Cancer Center Leman, Lausanne, Switzerland.

4. Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.

5. Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

6. Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.

7. Broad Institute of Harvard and MIT, Cambridge, MA, USA.

8. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

9. Massachusetts General Hospital Cancer Center, Charlestown, MA, USA.

10. Department of Medical Oncology, Heidelberg University Hospital, Heidelberg, Germany.

11. Department of Oncology, Center for Experimental Therapeutics, Lausanne University Hospital (CHUV), Lausanne, Switzerland.

12. Ludwig Institute for Cancer Research, Lausanne, Switzerland.

13. Department of Computational Biology, University of Lausanne (UNIL), Lausanne, Switzerland.

14. Swiss Institute of Bioinformatics, Lausanne, Switzerland.

15. Division of Clinical Pathology, Diagnostic Department, Geneva University Hospitals (HUG), Geneva, Switzerland.

16. Department of Otorhinolaryngology-Head and Neck Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland.

17. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

18. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.

19. Department of Systems Biology, Harvard Medical School, Boston, MA, USA.

20. Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.

21. Department of Otolaryngology Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.

22. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3