Bill and Wirapati et al. asked if common TME cellular processes control complex and variable patient outcomes. Single-cell analysis of 52 head and neck squamous cell carcinomas revealed tumor-associated macrophages (TAMs) were major contributors to patient outcomes, and TAM polarity, defined by the ratio of CXCL9 and SPP1 (CS) expression, but not by M1 or M2 markers, had strong prognostic association. CS TAM polarity was increased by IFNγ and decreased by hypoxia. Patients with CXCL9hi TAMs had better outcomes than patients with SPP1hi TAMs. CS TAM polarity identified co-regulated networks of cellular programs in the TMEs of various human cancers.
Contributed by Katherine Turner
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.
Author Info: (1) Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. Swiss Cancer Center Leman, Lausanne, Swi
Author Info: (1) 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. (2) Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. Swiss Cancer Center Leman, Lausanne, Switzerland. (3) 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. (4) Broad Institute of Harvard and MIT, Cambridge, MA, USA. (5) Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. Swiss Cancer Center Leman, Lausanne, Switzerland. (6) Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. Swiss Cancer Center Leman, Lausanne, Switzerland. (7) Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. Swiss Cancer Center Leman, Lausanne, Switzerland. (8) Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Massachusetts General Hospital Cancer Center, Charlestown, MA, USA. (9) Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA. (10) 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. (11) 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. (12) Department of Oncology, Center for Experimental Therapeutics, Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne, Switzerland. (13) 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. (14) 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. (15) Swiss Cancer Center Leman, Lausanne, Switzerland. Department of Computational Biology, University of Lausanne (UNIL), Lausanne, Switzerland. Swiss Institute of Bioinformatics, Lausanne, Switzerland. (16) 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. (17) Division of Clinical Pathology, Diagnostic Department, Geneva University Hospitals (HUG), Geneva, Switzerland. (18) Department of Otorhinolaryngology-Head and Neck Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland. (19) Department of Otorhinolaryngology-Head and Neck Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland. (20) Broad Institute of Harvard and MIT, Cambridge, MA, USA. Massachusetts General Hospital Cancer Center, Charlestown, MA, USA. (21) Broad Institute of Harvard and MIT, Cambridge, MA, USA. Massachusetts General Hospital Cancer Center, Charlestown, MA, USA. (22) Broad Institute of Harvard and MIT, Cambridge, MA, USA. Massachusetts General Hospital Cancer Center, Charlestown, MA, USA. (23) Broad Institute of Harvard and MIT, Cambridge, MA, USA. Massachusetts General Hospital Cancer Center, Charlestown, MA, USA. (24) 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. (25) 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. (26) Department of Systems Biology, Harvard Medical School, Boston, MA, USA. (27) 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. (28) 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. (29) 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. (30) Department of Otolaryngology Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA. (31) 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. (32) Broad Institute of Harvard and MIT, Cambridge, MA, USA. Massachusetts General Hospital Cancer Center, Charlestown, MA, USA. (33) 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.
