Pan-cancer analysis of genomic properties and clinical outcome associated with tumor tertiary lymphoid structure

Abstract How the genomic landscape of a tumor shapes the formation of tertiary lymphoid structure (TLS) and how might TLS alter the clinical outcome or response to immunotherapy had not been systematically explored. Utilizing the genomic and transcriptome data of solid tumors on TCGA, we quantified...

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Autores principales:	Ziying Lin, Lixia Huang, ShaoLi Li, Jincui Gu, Xiaoxian Cui, Yanbin Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/28125f730e6c4ecfa912e3a8af52d5a8
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spelling	oai:doaj.org-article:28125f730e6c4ecfa912e3a8af52d5a82021-12-02T12:33:04ZPan-cancer analysis of genomic properties and clinical outcome associated with tumor tertiary lymphoid structure10.1038/s41598-020-78560-32045-2322https://doaj.org/article/28125f730e6c4ecfa912e3a8af52d5a82020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78560-3https://doaj.org/toc/2045-2322Abstract How the genomic landscape of a tumor shapes the formation of tertiary lymphoid structure (TLS) and how might TLS alter the clinical outcome or response to immunotherapy had not been systematically explored. Utilizing the genomic and transcriptome data of solid tumors on TCGA, we quantified TLS based on a previous identified 12-chemokine signature and evaluated its correlation with mutation/neoantigen burden, functional mutation of oncogenes and the presence of viral infection. Clinical data was integrated to decide the prognostic significance of TLS for different cancers after surgical treatment. Publicly available data (clinical and transcriptome data) of immunotherapy clinical trials involving melanoma and lung cancer were also collected to evaluate TLS’s association with therapeutic outcome. Mutation burden and predicted neoantigen counts were positively correlated with TLS scoring in multiple cancer types. Mutation in tumor suppressor genes (KEAP1, PBRM1) and genes involved in extrinsic apoptosis (CASP8), antigen-presentation (HLA-A, HLA-B), immune regulation (SMAD4) or DNA repair (BRCA1, BRCA2, TP53BP1) correlated with TLS alteration in multiple tumor types, indicating the interaction between mutation landscape and TLS formation. Epstein-Barr virus (EBV) infection in gastric cancer and human papillomavirus (HPV) infection in Head and Neck squamous cell carcinoma were associated with increased TLS scoring. High TLS scoring predicted favorable prognosis in certain cancer after surgical treatment and improved response to immunotherapy in lung cancer and melanoma. Our findings unraveled the genomic properties associated with TLS formation in different solid tumors and highlighted the prognostic and predictive significance of TLS in surgical treatment and immunotherapy.Ziying LinLixia HuangShaoLi LiJincui GuXiaoxian CuiYanbin ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ziying Lin Lixia Huang ShaoLi Li Jincui Gu Xiaoxian Cui Yanbin Zhou Pan-cancer analysis of genomic properties and clinical outcome associated with tumor tertiary lymphoid structure
description	Abstract How the genomic landscape of a tumor shapes the formation of tertiary lymphoid structure (TLS) and how might TLS alter the clinical outcome or response to immunotherapy had not been systematically explored. Utilizing the genomic and transcriptome data of solid tumors on TCGA, we quantified TLS based on a previous identified 12-chemokine signature and evaluated its correlation with mutation/neoantigen burden, functional mutation of oncogenes and the presence of viral infection. Clinical data was integrated to decide the prognostic significance of TLS for different cancers after surgical treatment. Publicly available data (clinical and transcriptome data) of immunotherapy clinical trials involving melanoma and lung cancer were also collected to evaluate TLS’s association with therapeutic outcome. Mutation burden and predicted neoantigen counts were positively correlated with TLS scoring in multiple cancer types. Mutation in tumor suppressor genes (KEAP1, PBRM1) and genes involved in extrinsic apoptosis (CASP8), antigen-presentation (HLA-A, HLA-B), immune regulation (SMAD4) or DNA repair (BRCA1, BRCA2, TP53BP1) correlated with TLS alteration in multiple tumor types, indicating the interaction between mutation landscape and TLS formation. Epstein-Barr virus (EBV) infection in gastric cancer and human papillomavirus (HPV) infection in Head and Neck squamous cell carcinoma were associated with increased TLS scoring. High TLS scoring predicted favorable prognosis in certain cancer after surgical treatment and improved response to immunotherapy in lung cancer and melanoma. Our findings unraveled the genomic properties associated with TLS formation in different solid tumors and highlighted the prognostic and predictive significance of TLS in surgical treatment and immunotherapy.
format	article
author	Ziying Lin Lixia Huang ShaoLi Li Jincui Gu Xiaoxian Cui Yanbin Zhou
author_facet	Ziying Lin Lixia Huang ShaoLi Li Jincui Gu Xiaoxian Cui Yanbin Zhou
author_sort	Ziying Lin
title	Pan-cancer analysis of genomic properties and clinical outcome associated with tumor tertiary lymphoid structure
title_short	Pan-cancer analysis of genomic properties and clinical outcome associated with tumor tertiary lymphoid structure
title_full	Pan-cancer analysis of genomic properties and clinical outcome associated with tumor tertiary lymphoid structure
title_fullStr	Pan-cancer analysis of genomic properties and clinical outcome associated with tumor tertiary lymphoid structure
title_full_unstemmed	Pan-cancer analysis of genomic properties and clinical outcome associated with tumor tertiary lymphoid structure
title_sort	pan-cancer analysis of genomic properties and clinical outcome associated with tumor tertiary lymphoid structure
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/28125f730e6c4ecfa912e3a8af52d5a8
work_keys_str_mv	AT ziyinglin pancanceranalysisofgenomicpropertiesandclinicaloutcomeassociatedwithtumortertiarylymphoidstructure AT lixiahuang pancanceranalysisofgenomicpropertiesandclinicaloutcomeassociatedwithtumortertiarylymphoidstructure AT shaolili pancanceranalysisofgenomicpropertiesandclinicaloutcomeassociatedwithtumortertiarylymphoidstructure AT jincuigu pancanceranalysisofgenomicpropertiesandclinicaloutcomeassociatedwithtumortertiarylymphoidstructure AT xiaoxiancui pancanceranalysisofgenomicpropertiesandclinicaloutcomeassociatedwithtumortertiarylymphoidstructure AT yanbinzhou pancanceranalysisofgenomicpropertiesandclinicaloutcomeassociatedwithtumortertiarylymphoidstructure
_version_	1718393848538857472

Pan-cancer analysis of genomic properties and clinical outcome associated with tumor tertiary lymphoid structure

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