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The T cell differentiation landscape is shaped by tumour mutations in lung cancer.
Ghorani, Ehsan; Reading, James L; Henry, Jake Y; Massy, Marc Robert de; Rosenthal, Rachel; Turati, Virginia; Joshi, Kroopa; Furness, Andrew J S; Ben Aissa, Assma; Saini, Sunil Kumar; Ramskov, Sofie; Georgiou, Andrew; Sunderland, Mariana Werner; Wong, Yien Ning Sophia; Mucha, Maria Vila De; Day, William; Galvez-Cancino, Felipe; Becker, Pablo D; Uddin, Imran; Oakes, Theres; Ismail, Mazlina; Ronel, Tahel; Woolston, Annemarie; Jamal-Hanjani, Mariam; Veeriah, Selvaraju; Birkbak, Nicolai J; Wilson, Gareth A; Litchfield, Kevin; Conde, Lucia; Guerra-Assunção, José Afonso; Blighe, Kevin; Biswas, Dhruva; Salgado, Roberto; Lund, Tom; Bakir, Maise Al; Moore, David A; Hiley, Crispin T; Loi, Sherene; Sun, Yuxin; Yuan, Yinyin; AbdulJabbar, Khalid; Turajilic, Samra; Herrero, Javier; Enver, Tariq; Hadrup, Sine R; Hackshaw, Allan; Peggs, Karl S; McGranahan, Nicholas; Chain, Benny; Swanton, Charles.
Afiliação
  • Ghorani E; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • Reading JL; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Henry JY; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK. j.reading@ucl.ac.uk.
  • Massy MR; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. j.reading@ucl.ac.uk.
  • Rosenthal R; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • Turati V; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Joshi K; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • Furness AJS; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Ben Aissa A; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Saini SK; Department of Cancer Biology, University College London Cancer Institute, London, UK.
  • Ramskov S; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • Georgiou A; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Sunderland MW; Department of Medical Oncology, The Royal Marsden NHS Foundation Trust, London, UK.
  • Wong YNS; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • Mucha MV; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Day W; Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.
  • Galvez-Cancino F; Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.
  • Becker PD; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • Uddin I; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Oakes T; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • Ismail M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Ronel T; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • Woolston A; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Jamal-Hanjani M; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • Veeriah S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Birkbak NJ; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • Wilson GA; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Litchfield K; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • Conde L; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Guerra-Assunção JA; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • Blighe K; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Biswas D; Division of Infection and Immunity, University College London, London, UK.
  • Salgado R; Division of Infection and Immunity, University College London, London, UK.
  • Lund T; Division of Infection and Immunity, University College London, London, UK.
  • Bakir MA; Division of Infection and Immunity, University College London, London, UK.
  • Moore DA; Division of Infection and Immunity, University College London, London, UK.
  • Hiley CT; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Loi S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Sun Y; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Yuan Y; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • AbdulJabbar K; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Turajilic S; Bill Lyons Informatics Centre, University College London Cancer Institute, London, UK.
  • Herrero J; Bill Lyons Informatics Centre, University College London Cancer Institute, London, UK.
  • Enver T; Bill Lyons Informatics Centre, University College London Cancer Institute, London, UK.
  • Hadrup SR; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Hackshaw A; Department of Pathology, GZA-ZNA, Antwerp, Belgium.
  • Peggs KS; Department of Medical Oncology, The Royal Marsden NHS Foundation Trust, London, UK.
  • McGranahan N; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Chain B; Department of Pathology, University College London Cancer Institute, London, UK.
  • Swanton C; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Nat Cancer ; 1(5): 546-561, 2020 05.
Article em En | MEDLINE | ID: mdl-32803172
Tumour mutational burden (TMB) predicts immunotherapy outcome in non-small cell lung cancer (NSCLC), consistent with immune recognition of tumour neoantigens. However, persistent antigen exposure is detrimental for T cell function. How TMB affects CD4 and CD8 T cell differentiation in untreated tumours, and whether this affects patient outcomes is unknown. Here we paired high-dimensional flow cytometry, exome, single-cell and bulk RNA sequencing from patients with resected, untreated NSCLC to examine these relationships. TMB was associated with compartment-wide T cell differentiation skewing, characterized by loss of TCF7-expressing progenitor-like CD4 T cells, and an increased abundance of dysfunctional CD8 and CD4 T cell subsets, with significant phenotypic and transcriptional similarity to neoantigen-reactive CD8 T cells. A gene signature of redistribution from progenitor-like to dysfunctional states associated with poor survival in lung and other cancer cohorts. Single-cell characterization of these populations informs potential strategies for therapeutic manipulation in NSCLC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Cancer Ano de publicação: 2020 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Cancer Ano de publicação: 2020 Tipo de documento: Article