Neoantigen-directed immune escape in lung cancer evolution.

Adenocarcinoma / genetics Antigen Presentation / immunology Antigens, Neoplasm / genetics Carcinoma, Non-Small-Cell Lung / genetics Carcinoma, Squamous Cell / genetics Disease-Free Survival Evolution, Molecular Female Gene Expression Regulation, Neoplastic / genetics Humans Lung Neoplasms / genetics Lymphocytes, Tumor-Infiltrating / immunology Male Prognosis Tumor Escape / immunology Tumor Microenvironment / immunology

Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
03 2019
Historique:
received: 17 08 2018
accepted: 21 02 2019
pubmed: 22 3 2019
medline: 29 10 2019
entrez: 22 3 2019
Statut: ppublish

Résumé

The interplay between an evolving cancer and a dynamic immune microenvironment remains unclear. Here we analyse 258 regions from 88 early-stage, untreated non-small-cell lung cancers using RNA sequencing and histopathology-assessed tumour-infiltrating lymphocyte estimates. Immune infiltration varied both between and within tumours, with different mechanisms of neoantigen presentation dysfunction enriched in distinct immune microenvironments. Sparsely infiltrated tumours exhibited a waning of neoantigen editing during tumour evolution, indicative of historical immune editing, or copy-number loss of previously clonal neoantigens. Immune-infiltrated tumour regions exhibited ongoing immunoediting, with either loss of heterozygosity in human leukocyte antigens or depletion of expressed neoantigens. We identified promoter hypermethylation of genes that contain neoantigenic mutations as an epigenetic mechanism of immunoediting. Our results suggest that the immune microenvironment exerts a strong selection pressure in early-stage, untreated non-small-cell lung cancers that produces multiple routes to immune evasion, which are clinically relevant and forecast poor disease-free survival.

Identifiants

DOI: 10.1038/s41586-019-1032-7 PMID: 30894752 PMC: PMC6954100
pubmed: 30894752
doi: 10.1038/s41586-019-1032-7
pii: 10.1038/s41586-019-1032-7
pmc: PMC6954100
mid: EMS85285
doi:

Substances chimiques

Antigens, Neoplasm 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

479-485

Subventions

Organisme : Medical Research Council
ID : FC001169
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001169
Pays : United Kingdom
Organisme : European Research Council
Pays : International
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : Medical Research Council
ID : MC_UP_1203/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001202
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A20764
Pays : United Kingdom
Organisme : Worldwide Cancer Research
ID : 13-0316
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001202
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001169
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A22246
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001202
Pays : United Kingdom

Investigateurs

Charles Swanton (C)
Mariam Jamal-Hanjani (M)
Selvaraju Veeriah (S)
Justyna Czyzewska-Khan (J)
Diana Johnson (D)
Joanne Laycock (J)
Rachel Rosenthal (R)
Pat Gorman (P)
Robert E Hynds (RE)
Gareth Wilson (G)
Nicolai J Birkbak (NJ)
Thomas B K Watkins (TBK)
Nicholas McGranahan (N)
Mickael Escudero (M)
Aengus Stewart (A)
Peter Van Loo (P)
Andrew Rowan (A)
Crispin Hiley (C)
Christopher Abbosh (C)
Jacki Goldman (J)
Richard Kevin Stone (RK)
Tamara Denner (T)
Sophia Ward (S)
Emma Nye (E)
Kroopa Joshi (K)
Assma Ben Aissa (A)
Yien Ning Sophia Wong (YNS)
Andy Georgiou (A)
Sergio Quezada (S)
John A Hartley (JA)
Helen L Lowe (HL)
Javier Herrero (J)
David Lawrence (D)
Martin Hayward (M)
Nikolaos Panagiotopoulos (N)
Mary Falzon (M)
Elaine Borg (E)
Teresa Marafioti (T)
Sam M Janes (SM)
Martin Forster (M)
Tanya Ahmad (T)
Siow Ming Lee (SM)
Dionysis Papadatos-Pastos (D)
Dawn Carnell (D)
Ruheena Mendes (R)
Jeremy George (J)
Asia Ahmed (A)
Magali Taylor (M)
Junaid Choudhary (J)
Yvonne Summers (Y)
Raffaele Califano (R)
Paul Taylor (P)
Rajesh Shah (R)
Piotr Krysiak (P)
Kendadai Rammohan (K)
Eustace Fontaine (E)
Richard Booton (R)
Matthew Evison (M)
Phil Crosbie (P)
Stuart Moss (S)
Leena Joseph (L)
Paul Bishop (P)
Anne Marie Quinn (AM)
Helen Doran (H)
Angela Leek (A)
Phil Harrison (P)
Katrina Moore (K)
Rachael Waddington (R)
Juliette Novasio (J)
Fiona Blackhall (F)
Jane Rogan (J)
Elaine Smith (E)
Caroline Dive (C)
Jonathan Tugwood (J)
Ged Brady (G)
Dominic G Rothwell (DG)
Jackie Pierce (J)
Sakshi Gulati (S)
Babu Naidu (B)
Gerald Langman (G)
Simon Trotter (S)
Hollie Bancroft (H)
Amy Kerr (A)
Salma Kadiri (S)
Gary Middleton (G)
Madava Djearaman (M)
Dean Fennell (D)
Jacqui A Shaw (JA)
John Le Quesne (J)
David A Moore (DA)
Apostolos Nakas (A)
Sridhar Rathinam (S)
William Monteiro (W)
Hilary Marshall (H)
Louise Nelson (L)
Joan Riley (J)
Lindsay Primrose (L)
Luke Martinson (L)
Girija Anand (G)
Sajid Khan (S)
Marianne Nicolson (M)
Keith Kerr (K)
Shirley Palmer (S)
Hardy Remmen (H)
Joy Miller (J)
Keith Buchan (K)
Mahendran Chetty (M)
Lesley Gomersall (L)
Jason Lester (J)
Fiona Morgan (F)
Haydn Adams (H)
Helen Davies (H)
Malgorzata Kornaszewska (M)
Richard Attanoos (R)
Sara Lock (S)
Mairead MacKenzie (M)
Maggie Wilcox (M)
Harriet Bell (H)
Allan Hackshaw (A)
Yenting Ngai (Y)
Sean Smith (S)
Nicole Gower (N)
Christian Ottensmeier (C)
Serena Chee (S)
Benjamin Johnson (B)
Aiman Alzetani (A)
Emily Shaw (E)
Eric Lim (E)
Paulo De Sousa (P)
Monica Tavares Barbosa (MT)
Alex Bowman (A)
Simon Jordan (S)
Alexandra Rice (A)
Hilgardt Raubenheimer (H)
Harshil Bhayani (H)
Morag Hamilton (M)
Natalie Mensah (N)
Lyn Ambrose (L)
Anand Devaraj (A)
Hema Chavan (H)
Andrew G Nicholson (AG)
Kelvin Lau (K)
Michael Sheaff (M)
Peter Schmid (P)
John Conibear (J)
Veni Ezhil (V)
Vineet Prakash (V)
Peter Russell (P)
Teresa Light (T)
Tracey Horey (T)
Sarah Danson (S)
Jonathan Bury (J)
John Edwards (J)
Jennifer Hill (J)
Sue Matthews (S)
Yota Kitsanta (Y)
Kim Suvarna (K)
Patricia Fisher (P)
Michael Shackcloth (M)
John Gosney (J)
Sarah Feeney (S)
Julius Asante-Siaw (J)
Kim Ryanna (K)
Alan Dawson (A)
Mohamad Tuffail (M)
Amrita Bajaj (A)
Jan Brozik (J)
Harriet Walter (H)
Nicolas Carey (N)
Gillian Price (G)
Kayleigh Gilbert (K)
Joanne Webb (J)
Akshay Patel (A)
Anshuman Chaturvedi (A)
Felice Granato (F)
Katie Baker (K)
Mathew Carter (M)
Lynsey Priest (L)
Matthew G Krebs (MG)
Colin Lindsay (C)
Fabio Gomes (F)
Francesca Chemie (F)
Robert George (R)
Davide Patrini (D)
Reena Khiroya (R)
Penny Shaw (P)
Marcin Skrzypski (M)
Mariana Werner Sunderland (MW)
James L Reading (JL)
Carmella Beastall (C)
Nagina Mangal (N)
Karl Peggs (K)
Emilia Lim (E)
Maise Al-Bakir (M)
Neal Navani (N)
Marco Scarci (M)
Leah Ensell (L)
Dhruva Biswas (D)
Roberto Salgado (R)
Maryam Razaq (M)
Jerome Nicod (J)
Stephan Beck (S)
Saioa Lopez (S)
Ariana Huebner (A)
Michelle Dietzen (M)
Thanos Mourikis (T)
Toyin Adefila-Ideozu (T)
Sofina Begum (S)
Henriette Klein (H)
Aleksander Mani (A)
Soraia Carvalho (S)
Daniel Kaniu (D)
Cristina Realingo (C)
Mpho Malima (M)
Sarah Booth (S)
Louise Lim (L)
Jagan Rao (J)
Sara Tenconi (S)
Laura Socci (L)
Faith Kibutu (F)
Michael Agyemang (M)
Robin Young (R)
Kevin G Blyth (KG)
Craig Dick (C)
Alan Kirk (A)
Andrew Kidd (A)

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn

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Auteurs

Rachel Rosenthal (R)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK.
Bill Lyons Informatics Centre, University College London Cancer Institute, University College London, London, UK.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.

Elizabeth Larose Cadieux (EL)

Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.

Roberto Salgado (R)

Department of Pathology, GZA-ZNA, Antwerp, Belgium.
Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.

Maise Al Bakir (MA)

Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.

David A Moore (DA)

Department of Pathology, University College London Cancer Institute, University College London, London, UK.

Crispin T Hiley (CT)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.

Tom Lund (T)

Cancer Immunology Unit, University College London Cancer Institute, University College London, London, UK.
Research Department of Haematology, University College London Cancer Institute, University College London, London, UK.

Miljana Tanić (M)

Department of Cancer Biology, University College London Cancer Institute, University College London, London, UK.

James L Reading (JL)

Cancer Immunology Unit, University College London Cancer Institute, University College London, London, UK.
Research Department of Haematology, University College London Cancer Institute, University College London, London, UK.

Kroopa Joshi (K)

Cancer Immunology Unit, University College London Cancer Institute, University College London, London, UK.
Research Department of Haematology, University College London Cancer Institute, University College London, London, UK.

Jake Y Henry (JY)

Cancer Immunology Unit, University College London Cancer Institute, University College London, London, UK.
Research Department of Haematology, University College London Cancer Institute, University College London, London, UK.

Ehsan Ghorani (E)

Cancer Immunology Unit, University College London Cancer Institute, University College London, London, UK.
Research Department of Haematology, University College London Cancer Institute, University College London, London, UK.

Gareth A Wilson (GA)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.

Nicolai J Birkbak (NJ)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.

Mariam Jamal-Hanjani (M)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK.

Selvaraju Veeriah (S)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK.

Zoltan Szallasi (Z)

Computational Health Informatics Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Danish Cancer Society Research Center, Copenhagen, Denmark.

Sherene Loi (S)

Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.

Matthew D Hellmann (MD)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Weill Cornell Medical College, Cornell University, New York, NY, USA.

Andrew Feber (A)

Division of Surgery and Interventional Science, University College London, London, UK.

Benny Chain (B)

Division of Infection and Immunity, University College London, London, UK.
Department of Computer Sciences, University College London, London, UK.

Javier Herrero (J)

Bill Lyons Informatics Centre, University College London Cancer Institute, University College London, London, UK.

Sergio A Quezada (SA)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK.
Cancer Immunology Unit, University College London Cancer Institute, University College London, London, UK.
Research Department of Haematology, University College London Cancer Institute, University College London, London, UK.

Jonas Demeulemeester (J)

Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.
Department of Human Genetics, University of Leuven, Leuven, Belgium.

Peter Van Loo (P)

Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.
Department of Human Genetics, University of Leuven, Leuven, Belgium.

Stephan Beck (S)

Department of Cancer Biology, University College London Cancer Institute, University College London, London, UK.

Nicholas McGranahan (N)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK. Nicholas.McGranahan.10@ucl.ac.uk.
Cancer Genome Evolution Research Group, University College London Cancer Institute, University College London, London, UK. Nicholas.McGranahan.10@ucl.ac.uk.

Charles Swanton (C)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK. Charles.Swanton@crick.ac.uk.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK. Charles.Swanton@crick.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Carcinomes › Adénocarcinome › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité acquise › Immunité cellulaire › Présentation d'antigène › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes néoplasiques › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Tumeurs des bronches › Carcinome bronchogénique › Carcinome pulmonaire non à petites cellules › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Tumeurs épidermoïdes › Carcinome épidermoïde › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Survie sans rechute › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Phénomènes biologiques › Évolution biologique › Évolution moléculaire › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes TIL › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Diagnostic › Pronostic › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Phénomènes du système immunitaire › Échappement de la tumeur à la surveillance immunitaire › Neoantigen-directed immune escape in lung...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Neoantigen-directed immune escape in lung...