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Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy.
Gide, Tuba N; Quek, Camelia; Menzies, Alexander M; Tasker, Annie T; Shang, Ping; Holst, Jeff; Madore, Jason; Lim, Su Yin; Velickovic, Rebecca; Wongchenko, Matthew; Yan, Yibing; Lo, Serigne; Carlino, Matteo S; Guminski, Alexander; Saw, Robyn P M; Pang, Angel; McGuire, Helen M; Palendira, Umaimainthan; Thompson, John F; Rizos, Helen; Silva, Ines Pires da; Batten, Marcel; Scolyer, Richard A; Long, Georgina V; Wilmott, James S.
Afiliación
  • Gide TN; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
  • Quek C; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
  • Menzies AM; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Department of Medical Oncology, Royal North Shore Hospital, Sydney, NSW 2065, Australia; Department of Medical Oncology, Mater Hospital,
  • Tasker AT; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia.
  • Shang P; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia.
  • Holst J; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Centenary Institute, The University of Sydney, Sydney, NSW 2050, Australia.
  • Madore J; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia.
  • Lim SY; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
  • Velickovic R; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia.
  • Wongchenko M; Oncology Biomarker Development, Genentech Inc, South San Francisco, CA 94080, USA.
  • Yan Y; Oncology Biomarker Development, Genentech Inc, South San Francisco, CA 94080, USA.
  • Lo S; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia.
  • Carlino MS; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, NSW 2145, Australia.
  • Guminski A; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Department of Medical Oncology, Royal North Shore Hospital, Sydney, NSW 2065, Australia; Department of Medical Oncology, Mater Hospital,
  • Saw RPM; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
  • Pang A; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Centenary Institute, The University of Sydney, Sydney, NSW 2050, Australia.
  • McGuire HM; Ramaciotti Facility for Human Systems Biology, Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Discipline of Pathology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
  • Palendira U; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Centenary Institute, The University of Sydney, Sydney, NSW 2050, Australia.
  • Thompson JF; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
  • Rizos H; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
  • Silva IPD; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
  • Batten M; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
  • Scolyer RA; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
  • Long GV; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Department of Medical Oncology, Royal North Shore Hospital, Sydney, NSW 2065, Australia; Department of Medical Oncology, Mater Hospital,
  • Wilmott JS; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: james.wilmott@melanoma.org.au.
Cancer Cell ; 35(2): 238-255.e6, 2019 02 11.
Article en En | MEDLINE | ID: mdl-30753825
ABSTRACT
Cancer immunotherapies provide survival benefits in responding patients, but many patients fail to respond. Identifying the biology of treatment response and resistance are a priority to optimize drug selection and improve patient outcomes. We performed transcriptomic and immune profiling on 158 tumor biopsies from melanoma patients treated with anti-PD-1 monotherapy (n = 63) or combined anti-PD-1 and anti-CTLA-4 (n = 57). These data identified activated T cell signatures and T cell populations in responders to both treatments. Further mass cytometry analysis identified an EOMES+CD69+CD45RO+ effector memory T cell phenotype that was significantly more abundant in responders to combined immunotherapy compared with non-responders (n = 18). The gene expression profile of this population was associated with longer progression-free survival in patients treated with single agent and greater tumor shrinkage in both treatments.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Linfocitos T / Protocolos de Quimioterapia Combinada Antineoplásica / Linfocitos Infiltrantes de Tumor / Anticuerpos Monoclonales Humanizados / Antígeno CTLA-4 / Receptor de Muerte Celular Programada 1 / Ipilimumab / Antineoplásicos Inmunológicos / Nivolumab Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2019 Tipo del documento: Article País de afiliación: Australia
Texto completo
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Linfocitos T / Protocolos de Quimioterapia Combinada Antineoplásica / Linfocitos Infiltrantes de Tumor / Anticuerpos Monoclonales Humanizados / Antígeno CTLA-4 / Receptor de Muerte Celular Programada 1 / Ipilimumab / Antineoplásicos Inmunológicos / Nivolumab Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2019 Tipo del documento: Article País de afiliación: Australia