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CRISPR-Cas9 screening identifies an IRF1-SOCS1-mediated negative feedback loop that limits CXCL9 expression and antitumor immunity.
House, Imran G; Derrick, Emily B; Sek, Kevin; Chen, Amanda X Y; Li, Jasmine; Lai, Junyun; Todd, Kirsten L; Munoz, Isabelle; Michie, Jessica; Chan, Cheok Weng; Huang, Yu-Kuan; Chan, Jack D; Petley, Emma V; Tong, Junming; Nguyen, DatMinh; Engel, Sven; Savas, Peter; Hogg, Simon J; Vervoort, Stephin J; Kearney, Conor J; Burr, Marian L; Lam, Enid Y N; Gilan, Omer; Bedoui, Sammy; Johnstone, Ricky W; Dawson, Mark A; Loi, Sherene; Darcy, Phillip K; Beavis, Paul A.
Afiliação
  • House IG; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: imran.house@petermac.org.
  • Derrick EB; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Sek K; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Chen AXY; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Li J; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Lai J; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Todd KL; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Munoz I; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Michie J; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Chan CW; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Huang YK; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Chan JD; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Petley EV; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Tong J; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Nguyen D; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Engel S; Department of Microbiology and Immunology at the Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia; Institute of Experimental Immunology, University of Bonn, Bonn, Germany.
  • Savas P; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia.
  • Hogg SJ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia.
  • Vervoort SJ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia.
  • Kearney CJ; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, 3084, Australia; School of Cancer Medicine, La Trobe University, Melbourne, VIC, 3086, Australia.
  • Burr ML; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Austr
  • Lam EYN; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia.
  • Gilan O; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia.
  • Bedoui S; Department of Microbiology and Immunology at the Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia; Institute of Experimental Immunology, University of Bonn, Bonn, Germany.
  • Johnstone RW; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia.
  • Dawson MA; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia; Department of Haematology, Peter MacCallum Cancer Centre and The Royal Melbourne Hospital,
  • Loi S; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia.
  • Darcy PK; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Department of Immunology, Monash University, Clayton, VIC, Australia. Electronic address: phil.darcy@pete
  • Beavis PA; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: paul.beavis@petermac.org.
Cell Rep ; 42(8): 113014, 2023 08 29.
Article em En | MEDLINE | ID: mdl-37605534
ABSTRACT
CXCL9 expression is a strong predictor of response to immune checkpoint blockade therapy. Accordingly, we sought to develop therapeutic strategies to enhance the expression of CXCL9 and augment antitumor immunity. To perform whole-genome CRISPR-Cas9 screening for regulators of CXCL9 expression, a CXCL9-GFP reporter line is generated using a CRISPR knockin strategy. This approach finds that IRF1 limits CXCL9 expression in both tumor cells and primary myeloid cells through induction of SOCS1, which subsequently limits STAT1 signaling. Thus, we identify a subset of STAT1-dependent genes that do not require IRF1 for their transcription, including CXCL9. Targeting of either IRF1 or SOCS1 potently enhances CXCL9 expression by intratumoral macrophages, which is further enhanced in the context of immune checkpoint blockade therapy. We hence show a non-canonical role for IRF1 in limiting the expression of a subset of STAT1-dependent genes through induction of SOCS1.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sistemas CRISPR-Cas / Inibidores de Checkpoint Imunológico Tipo de estudo: Diagnostic_studies / Screening_studies Idioma: En Revista: Cell Rep Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sistemas CRISPR-Cas / Inibidores de Checkpoint Imunológico Tipo de estudo: Diagnostic_studies / Screening_studies Idioma: En Revista: Cell Rep Ano de publicação: 2023 Tipo de documento: Article