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IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment.
Nirschl, Christopher J; Suárez-Fariñas, Mayte; Izar, Benjamin; Prakadan, Sanjay; Dannenfelser, Ruth; Tirosh, Itay; Liu, Yong; Zhu, Qian; Devi, K Sanjana P; Carroll, Shaina L; Chau, David; Rezaee, Melika; Kim, Tae-Gyun; Huang, Ruiqi; Fuentes-Duculan, Judilyn; Song-Zhao, George X; Gulati, Nicholas; Lowes, Michelle A; King, Sandra L; Quintana, Francisco J; Lee, Young-Suk; Krueger, James G; Sarin, Kavita Y; Yoon, Charles H; Garraway, Levi; Regev, Aviv; Shalek, Alex K; Troyanskaya, Olga; Anandasabapathy, Niroshana.
Afiliação
  • Nirschl CJ; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Suárez-Fariñas M; Department of Dermatology, Mount Sinai School of Medicine, NY, NY 10029, USA; Department of Genetics and Genomics Sciences Mount Sinai School of Medicine, NY, NY 10029 USA; Population Health Science and Policy, Mount Sinai School of Medicine, NY, NY 10029, USA.
  • Izar B; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Prakadan S; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering and Science and Department of Chemistry, MIT, Cambridge, MA 02139, USA; Ragon Institute of MIT, Harvard, and MGH, Cambridge, MA 02139, USA.
  • Dannenfelser R; Department of Computer Science, Princeton University, Princeton, NJ 08540, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA.
  • Tirosh I; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Liu Y; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Zhu Q; Department of Computer Science, Princeton University, Princeton, NJ 08540, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA.
  • Devi KSP; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Carroll SL; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering and Science and Department of Chemistry, MIT, Cambridge, MA 02139, USA; Ragon Institute of MIT, Harvard, and MGH, Cambridge, MA 02139, USA.
  • Chau D; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Rezaee M; Department of Dermatology, Stanford University, Stanford, CA 94305, USA.
  • Kim TG; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Huang R; Department of Genetics and Genomics Sciences Mount Sinai School of Medicine, NY, NY 10029 USA.
  • Fuentes-Duculan J; Laboratory for Investigative Dermatology, Rockefeller University. New York, NY 10065, USA.
  • Song-Zhao GX; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Gulati N; Laboratory for Investigative Dermatology, Rockefeller University. New York, NY 10065, USA.
  • Lowes MA; Laboratory for Investigative Dermatology, Rockefeller University. New York, NY 10065, USA.
  • King SL; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Quintana FJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA 02458, USA.
  • Lee YS; Department of Computer Science, Princeton University, Princeton, NJ 08540, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA.
  • Krueger JG; Laboratory for Investigative Dermatology, Rockefeller University. New York, NY 10065, USA.
  • Sarin KY; Department of Dermatology, Stanford University, Stanford, CA 94305, USA.
  • Yoon CH; Department of Surgical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Surgical Oncology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Garraway L; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Ludwig Center at Harvard, Boston, MA 0
  • Regev A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Biology and Koch Institute, MIT, Boston, MA 02142, USA.
  • Shalek AK; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering and Science and Department of Chemistry, MIT, Cambridge, MA 02139, USA; Ragon Institute of MIT, Harvard, and MGH, Cambridge, MA 02139, USA; Division of Health Science & Technology, Harvard Medical Sch
  • Troyanskaya O; Department of Computer Science, Princeton University, Princeton, NJ 08540, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA; Simons Center for Data Analysis, Simons Foundation, New York, NY 10010, USA.
  • Anandasabapathy N; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Cancer Immunology and Melanoma, Harvard Cancer Center, Dana Farber Cancer Center, Boston, MA 02215, USA; Harvard Stem Cell Institute, Boston, MA 02115, USA. Electronic address: nanandasabapathy@pa
Cell ; 170(1): 127-141.e15, 2017 Jun 29.
Article em En | MEDLINE | ID: mdl-28666115
ABSTRACT
Homeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFNγ is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify survival. Single-cell RNA sequencing (RNA-seq) reveals enrichment of homeostatic modules in monocytes and DCs from human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFNγ. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T cells in vivo, indicating a critical regulatory role. These findings link immune homeostasis to key determinants of anti-tumoral immunity and escape, revealing co-opting of tissue-specific immune development in the tumor microenvironment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Monócitos / Interferon gama / Proteínas Supressoras da Sinalização de Citocina / Microambiente Tumoral / Melanoma / Metástase Neoplásica Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Monócitos / Interferon gama / Proteínas Supressoras da Sinalização de Citocina / Microambiente Tumoral / Melanoma / Metástase Neoplásica Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos