Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer.

Adult Aged Aged, 80 and over Carcinoma, Non-Small-Cell Lung / genetics DNA Copy Number Variations Female Genetic Heterogeneity HLA Antigens / genetics Humans Interferon-gamma / immunology Loss of Heterozygosity Lung Neoplasms / genetics Male Middle Aged Mutation Receptors, Antigen, T-Cell / genetics Signal Transduction / genetics Small Cell Lung Carcinoma / genetics Survival Analysis T-Lymphocytes / immunology Exome Sequencing

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
17 11 2021
Historique:
received: 10 06 2020
accepted: 25 10 2021
entrez: 18 11 2021
pubmed: 19 11 2021
medline: 16 12 2021
Statut: epublish

Résumé

Small-cell lung cancer (SCLC) is speculated to harbor complex genomic intratumor heterogeneity (ITH) associated with high recurrence rate and suboptimal response to immunotherapy. Here, using multi-region whole exome/T cell receptor (TCR) sequencing as well as immunohistochemistry, we reveal a rather homogeneous mutational landscape but extremely cold and heterogeneous TCR repertoire in limited-stage SCLC tumors (LS-SCLCs). Compared to localized non-small cell lung cancers, LS-SCLCs have similar predicted neoantigen burden and genomic ITH, but significantly colder and more heterogeneous TCR repertoire associated with higher chromosomal copy number aberration (CNA) burden. Furthermore, copy number loss of IFN-γ pathway genes is frequently observed and positively correlates with CNA burden. Higher mutational burden, higher T cell infiltration and positive PD-L1 expression are associated with longer overall survival (OS), while higher CNA burden is associated with shorter OS in patients with LS-SCLC.

Identifiants

DOI: 10.1038/s41467-021-26821-8 PMID: 34789716 PMC: PMC8599854
pubmed: 34789716
doi: 10.1038/s41467-021-26821-8
pii: 10.1038/s41467-021-26821-8
pmc: PMC8599854
doi:

Substances chimiques

HLA Antigens 0
IFNG protein, human 0
Receptors, Antigen, T-Cell 0
Interferon-gamma 82115-62-6

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6655

Subventions

Organisme : NCI NIH HHS
ID : U01 CA213273
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207295
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA070907
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009666
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA256780
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009302
Pays : United States

Informations de copyright

© 2021. The Author(s).

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Auteurs

Ming Chen (M)

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510060, China. chenming@sysucc.org.cn.
The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310022, China. chenming@sysucc.org.cn.
Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China. chenming@sysucc.org.cn.
Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang, 310022, China. chenming@sysucc.org.cn.

Runzhe Chen (R)

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510060, China.
Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Ying Jin (Y)

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310022, China.
Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang, 310022, China.

Jun Li (J)

Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Xin Hu (X)

Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Jiexin Zhang (J)

Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0001-9526-6730

Junya Fujimoto (J)

Department of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Shawna M Hubert (SM)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0002-7907-9609

Carl M Gay (CM)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0002-4907-0718

Bo Zhu (B)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Yanhua Tian (Y)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Nicholas McGranahan (N)

Cancer Research United Kingdom-University College London Lung Cancer Centre of Excellence, London, WC1E6BT, UK.
ORCID: 0000-0001-9537-4045

Won-Chul Lee (WC)

Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Julie George (J)

Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, 50931, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Cologne, 50937, Cologne, Germany.
ORCID: 0000-0002-4272-3683

Xiao Hu (X)

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310022, China.
Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang, 310022, China.

Yamei Chen (Y)

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310022, China.
Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang, 310022, China.

Meijuan Wu (M)

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310022, China.
Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang, 310022, China.

Carmen Behrens (C)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Chi-Wan Chow (CW)

Department of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Hoa H N Pham (HHN)

Department of Pathology, Nagasaki University Graduate school of Biomedical Sciences, Nagasaki, Japan.
ORCID: 0000-0002-0998-4486

Junya Fukuoka (J)

Department of Pathology, Nagasaki University Graduate school of Biomedical Sciences, Nagasaki, Japan.

Jia Wu (J)

Department of Image Physics, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0001-8392-8338

Edwin Roger Parra (ER)

Department of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0001-9068-1636

Latasha D Little (LD)

Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Curtis Gumbs (C)

Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Xingzhi Song (X)

Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Chang-Jiun Wu (CJ)

Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0001-8350-6397

Lixia Diao (L)

Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0001-6995-4492

Qi Wang (Q)

Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0003-0858-9393

Robert Cardnell (R)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Jianhua Zhang (J)

Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0001-5412-9860

Jing Wang (J)

Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0002-5398-0802

Xiuning Le (X)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0002-8554-1185

Don L Gibbons (DL)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0003-2362-3094

John V Heymach (JV)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0001-9068-8942

J Jack Lee (J)

Department of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0001-5469-9214

William N William (WN)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Chao Cheng (C)

Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, 77030, USA.
ORCID: 0000-0002-5002-3417

Bonnie Glisson (B)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Ignacio Wistuba (I)

Department of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

P Andrew Futreal (P)

Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
ORCID: 0000-0001-8663-2671

Roman K Thomas (RK)

Department of Translational Genomics, Medical Faculty, University of Cologne, Cologne, 50931, Germany. roman.thomas@uni-koeln.de.
Department of Pathology, Medical Faculty, University Hospital Cologne, Cologne, 50931, Germany. roman.thomas@uni-koeln.de.
DKFZ, German Cancer Research Center and German Cancer Consortium (DKTK), Heidelberg, 69115, Germany. roman.thomas@uni-koeln.de.

Alexandre Reuben (A)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA. areuben@mdanderson.org.
ORCID: 0000-0003-4510-0382

Lauren A Byers (LA)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA. lbyers@mdanderson.org.
ORCID: 0000-0002-0780-2677

Jianjun Zhang (J)

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA. jzhang20@mdanderson.org.
Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA. jzhang20@mdanderson.org.
ORCID: 0000-0001-7872-3477

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Cold and heterogeneous T cell repertoire is...
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 › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Hétérogénéité génétique › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Isoantigènes › Antigènes d'histocompatibilité › Antigènes HLA › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Lymphokines › Facteurs d'activation des macrophages › Interféron gamma › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Déséquilibre allélique › Perte d'hétérozygotie › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux antigènes › Récepteurs aux antigènes des cellules T › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Tumeurs des bronches › Carcinome bronchogénique › Carcinome pulmonaire à petites cellules › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Cold and heterogeneous T cell repertoire is...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Séquençage de l'exome › Cold and heterogeneous T cell repertoire is...