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Tim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity.
Chow, Andrew; Schad, Sara; Green, Michael D; Hellmann, Matthew D; Allaj, Viola; Ceglia, Nicholas; Zago, Giulia; Shah, Nisargbhai S; Sharma, Sai Kiran; Mattar, Marissa; Chan, Joseph; Rizvi, Hira; Zhong, Hong; Liu, Cailian; Bykov, Yonina; Zamarin, Dmitriy; Shi, Hongyu; Budhu, Sadna; Wohlhieter, Corrin; Uddin, Fathema; Gupta, Aditi; Khodos, Inna; Waninger, Jessica J; Qin, Angel; Markowitz, Geoffrey J; Mittal, Vivek; Balachandran, Vinod; Durham, Jennifer N; Le, Dung T; Zou, Weiping; Shah, Sohrab P; McPherson, Andrew; Panageas, Katherine; Lewis, Jason S; Perry, Justin S A; de Stanchina, Elisa; Sen, Triparna; Poirier, John T; Wolchok, Jedd D; Rudin, Charles M; Merghoub, Taha.
Afiliación
  • Chow A; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
  • Schad S; Weill Cornell Medical College, New York, NY, USA.
  • Green MD; Department of Radiation Oncology, University of Michigan Rogel Cancer Center and Veterans Affairs Ann Arbor Healthcare System, MI, USA.
  • Hellmann MD; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Allaj V; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Ceglia N; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Zago G; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Shah NS; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Sharma SK; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Mattar M; Antitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Chan J; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Rizvi H; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Zhong H; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Liu C; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Bykov Y; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Zamarin D; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
  • Shi H; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Budhu S; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Wohlhieter C; Weill Cornell Medical College, New York, NY, USA.
  • Uddin F; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Gupta A; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Khodos I; Antitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Waninger JJ; Department of Medical Education, University of Michigan School of Medicine, Ann Arbor, MI, USA.
  • Qin A; Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA.
  • Markowitz GJ; Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, NY, USA.
  • Mittal V; Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, NY, USA.
  • Balachandran V; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New
  • Durham JN; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Le DT; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Zou W; Departments of Surgery and Pathology, Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
  • Shah SP; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • McPherson A; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Panageas K; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Lewis JS; Weill Cornell Medical College, New York, NY, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Perry JSA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • de Stanchina E; Antitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Sen T; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Poirier JT; Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA.
  • Wolchok JD; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA; Parker Institute for Cancer Immunotherapy, Memorial
  • Rudin CM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: rudinc@mskcc.org.
  • Merghoub T; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA; Parker Institute for Cancer Immunotherapy, Memorial
Cancer Cell ; 39(7): 973-988.e9, 2021 07 12.
Article en En | MEDLINE | ID: mdl-34115989
Immune checkpoint blockade (ICB) has been a remarkable clinical advance for cancer; however, the majority of patients do not respond to ICB therapy. We show that metastatic disease in the pleural and peritoneal cavities is associated with poor clinical outcomes after ICB therapy. Cavity-resident macrophages express high levels of Tim-4, a receptor for phosphatidylserine (PS), and this is associated with reduced numbers of CD8+ T cells with tumor-reactive features in pleural effusions and peritoneal ascites from patients with cancer. We mechanistically demonstrate that viable and cytotoxic anti-tumor CD8+ T cells upregulate PS and this renders them susceptible to sequestration away from tumor targets and proliferation suppression by Tim-4+ macrophages. Tim-4 blockade abrogates this sequestration and proliferation suppression and enhances anti-tumor efficacy in models of anti-PD-1 therapy and adoptive T cell therapy in mice. Thus, Tim-4+ cavity-resident macrophages limit the efficacy of immunotherapies in these microenvironments.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Neoplasias del Colon / Linfocitos T CD8-positivos / Microambiente Tumoral / Macrófagos / Proteínas de la Membrana Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Neoplasias del Colon / Linfocitos T CD8-positivos / Microambiente Tumoral / Macrófagos / Proteínas de la Membrana Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos