Landscape of B cell immunity and related immune evasion in human cancers

Tumor-infiltrating B cells are an important component in the microenvironment but have unclear anti-tumor effects. We enhanced our previous computational algorithm TRUST to extract the B cell immunoglobulin hypervariable regions from bulk tumor RNA-sequencing data. TRUST assembled more than 30 milli...

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Published in:Nature genetics Vol. 51; no. 3; pp. 560 - 567
Main Authors: Hu, Xihao, Zhang, Jian, Wang, Jin, Fu, Jingxin, Li, Taiwen, Zheng, Xiaoqi, Wang, Binbin, Gu, Shengqing, Jiang, Peng, Fan, Jingyu, Ying, Xiaomin, Zhang, Jing, Carroll, Michael C., Wucherpfennig, Kai W., Hacohen, Nir, Zhang, Fan, Zhang, Peng, Liu, Jun S., Li, Bo, Liu, X. Shirley
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.03.2019
Nature Publishing Group
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ISSN:1061-4036, 1546-1718, 1546-1718
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Abstract Tumor-infiltrating B cells are an important component in the microenvironment but have unclear anti-tumor effects. We enhanced our previous computational algorithm TRUST to extract the B cell immunoglobulin hypervariable regions from bulk tumor RNA-sequencing data. TRUST assembled more than 30 million complementarity-determining region 3 sequences of the B cell heavy chain (IgH) from The Cancer Genome Atlas. Widespread B cell clonal expansions and immunoglobulin subclass switch events were observed in diverse human cancers. Prevalent somatic copy number alterations in the MICA and MICB genes related to antibody-dependent cell-mediated cytotoxicity were identified in tumors with elevated B cell activity. The IgG3–1 subclass switch interacts with B cell–receptor affinity maturation and defects in the antibody-dependent cell-mediated cytotoxicity pathway. Comprehensive pancancer analyses of tumor-infiltrating B cell–receptor repertoires identified novel tumor immune evasion mechanisms through genetic alterations. The IgH sequences identified here are potentially useful resources for future development of immunotherapies. This comprehensive pancancer analysis of RNA-sequencing data from bulk tumors defines the landscape of tumor-infiltrating B cell–receptor repertoires and highlights new mechanisms of tumor immune evasion through genetic alterations.
AbstractList Tumor-infiltrating B cells are an important component in the microenvironment with unclear anti-tumor impacts. We enhanced our previous computational algorithm TRUST to extract the B cell immunoglobulin (Ig) hypervariable regions from bulk tumor RNA-seq data. TRUST assembled over 30 million complementarity-determining region 3 (CDR3s) of the B cell heavy chain (IgH) from The Cancer Genome Atlas (TCGA). Widespread B cell clonal expansions and Ig subclass switch events were observed in diverse human cancers. Prevalent somatic copy number alterations in MICA and MICB genes related to antibody-dependent cell mediated cytotoxicity (ADCC) were identified in tumors with elevated B cell activity. IgG3-1 subclass switch interacts with the B cell receptor affinity maturation and defects in the ADCC pathway. Comprehensive pan-cancer analyses of tumor-infiltrating B cell receptor repertoires identified novel tumor immune evasion mechanisms through genetic alterations. The IgH sequences identified here are potentially useful resources for future development of immunotherapies. This comprehensive pan-cancer analysis of RNA sequencing data from bulk tumors defines the landscape of tumor-infiltrating B cell receptor repertoires and highlights new mechanisms of tumor immune evasion through genetic alterations.
Tumor-infiltrating B cells are an important component in the microenvironment but have unclear anti-tumor effects. We enhanced our previous computational algorithm TRUST to extract the B cell immunoglobulin hypervariable regions from bulk tumor RNA-sequencing data. TRUST assembled more than 30 million complementarity-determining region 3 sequences of the B cell heavy chain (IgH) from The Cancer Genome Atlas. Widespread B cell clonal expansions and immunoglobulin subclass switch events were observed in diverse human cancers. Prevalent somatic copy number alterations in the MICA and MICB genes related to antibody-dependent cell-mediated cytotoxicity were identified in tumors with elevated B cell activity. The IgG3–1 subclass switch interacts with B cell–receptor affinity maturation and defects in the antibody-dependent cell-mediated cytotoxicity pathway. Comprehensive pancancer analyses of tumor-infiltrating B cell–receptor repertoires identified novel tumor immune evasion mechanisms through genetic alterations. The IgH sequences identified here are potentially useful resources for future development of immunotherapies. This comprehensive pancancer analysis of RNA-sequencing data from bulk tumors defines the landscape of tumor-infiltrating B cell–receptor repertoires and highlights new mechanisms of tumor immune evasion through genetic alterations.
Tumor-infiltrating B cells are an important component in the microenvironment but have unclear anti-tumor effects. We enhanced our previous computational algorithm TRUST to extract the B cell immunoglobulin hypervariable regions from bulk tumor RNA-sequencing data. TRUST assembled more than 30 million complementarity-determining region 3 sequences of the B cell heavy chain (IgH) from The Cancer Genome Atlas. Widespread B cell clonal expansions and immunoglobulin subclass switch events were observed in diverse human cancers. Prevalent somatic copy number alterations in the MICA and MICB genes related to antibody-dependent cell-mediated cytotoxicity were identified in tumors with elevated B cell activity. The IgG3-1 subclass switch interacts with B cell-receptor affinity maturation and defects in the antibody-dependent cell-mediated cytotoxicity pathway. Comprehensive pancancer analyses of tumor-infiltrating B cell-receptor repertoires identified novel tumor immune evasion mechanisms through genetic alterations. The IgH sequences identified here are potentially useful resources for future development of immunotherapies.
Tumor-infiltrating B cells are an important component in the microenvironment but have unclear anti-tumor effects. We enhanced our previous computational algorithm TRUST to extract the B cell immunoglobulin hypervariable regions from bulk tumor RNA-sequencing data. TRUST assembled more than 30 million complementarity-determining region 3 sequences of the B cell heavy chain (IgH) from The Cancer Genome Atlas. Widespread B cell clonal expansions and immunoglobulin subclass switch events were observed in diverse human cancers. Prevalent somatic copy number alterations in the MICA and MICB genes related to antibody-dependent cell-mediated cytotoxicity were identified in tumors with elevated B cell activity. The IgG3-1 subclass switch interacts with B cell-receptor affinity maturation and defects in the antibody-dependent cell-mediated cytotoxicity pathway. Comprehensive pancancer analyses of tumor-infiltrating B cell-receptor repertoires identified novel tumor immune evasion mechanisms through genetic alterations. The IgH sequences identified here are potentially useful resources for future development of immunotherapies.Tumor-infiltrating B cells are an important component in the microenvironment but have unclear anti-tumor effects. We enhanced our previous computational algorithm TRUST to extract the B cell immunoglobulin hypervariable regions from bulk tumor RNA-sequencing data. TRUST assembled more than 30 million complementarity-determining region 3 sequences of the B cell heavy chain (IgH) from The Cancer Genome Atlas. Widespread B cell clonal expansions and immunoglobulin subclass switch events were observed in diverse human cancers. Prevalent somatic copy number alterations in the MICA and MICB genes related to antibody-dependent cell-mediated cytotoxicity were identified in tumors with elevated B cell activity. The IgG3-1 subclass switch interacts with B cell-receptor affinity maturation and defects in the antibody-dependent cell-mediated cytotoxicity pathway. Comprehensive pancancer analyses of tumor-infiltrating B cell-receptor repertoires identified novel tumor immune evasion mechanisms through genetic alterations. The IgH sequences identified here are potentially useful resources for future development of immunotherapies.
Tumor-infiltrating B cells are an important component in the microenvironment but have unclear anti-tumor effects. We enhanced our previous computational algorithm TRUST to extract the B cell immunoglobulin hypervariable regions from bulk tumor RNA-sequencing data. TRUST assembled more than 30 million complementarity-determining region 3 sequences of the B cell heavy chain (IgH) from The Cancer Genome Atlas. Widespread B cell clonal expansions and immunoglobulin subclass switch events were observed in diverse human cancers. Prevalent somatic copy number alterations in the MICA and MICB genes related to antibody-dependent cell-mediated cytotoxicity were identified in tumors with elevated B cell activity. The IgG3-1 subclass switch interacts with B cell-receptor affinity maturation and defects in the antibody-dependent cell-mediated cytotoxicity pathway. Comprehensive pancancer analyses of tumor-infiltrating B cell-receptor repertoires identified novel tumor immune evasion mechanisms through genetic alterations. The IgH sequences identified here are potentially useful resources for future development of immunotherapies. This comprehensive pancancer analysis of RNA-sequencing data from bulk tumors defines the landscape of tumor-infiltrating B cell-receptor repertoires and highlights new mechanisms of tumor immune evasion through genetic alterations.
Audience Academic
Author Gu, Shengqing
Zhang, Peng
Liu, X. Shirley
Wang, Binbin
Zhang, Jian
Hacohen, Nir
Li, Taiwen
Zhang, Fan
Zhang, Jing
Li, Bo
Zheng, Xiaoqi
Carroll, Michael C.
Wucherpfennig, Kai W.
Liu, Jun S.
Ying, Xiaomin
Jiang, Peng
Wang, Jin
Fu, Jingxin
Fan, Jingyu
Hu, Xihao
AuthorAffiliation 1 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
8 Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
7 Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
4 State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
5 Department of Mathematics, Shanghai Normal University, Shanghai, China
3 Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China
9 Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
6 Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, Massachusetts, USA
10 Statistics Department, Harvard University, Cambridg
AuthorAffiliation_xml – name: 4 State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
– name: 12 These authors contributed equally to this work
– name: 5 Department of Mathematics, Shanghai Normal University, Shanghai, China
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– name: 8 Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
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– name: 10 Statistics Department, Harvard University, Cambridge, Massachusetts, USA
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  organization: Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Department of Statistics, Harvard University
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30742113$$D View this record in MEDLINE/PubMed
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Copyright The Author(s), under exclusive licence to Springer Nature America, Inc. 2019
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B.L. conceived this project, modified TRUST codes to assemble B cell CDR3 sequences, and analyzed TCGA data. X.H. and J.Z. accelerated the TRUST codes, performed the validation analyses, and tested the clustering method. J.W., J.Fu, and T.L. helped with figures and data analyses, and B.W. and J.Fan helped generate intermediate data. P.Z. provided tumor samples, and S.G., F.Z., and X.Z. performed the BCR-seq and RNA-seq validation experiments. P.J., X.Y., J.Z., M.C.C., K.W.W., and N.H. provided expertise in immune evasive mechanisms and data analysis. J.S.L. and X.S.L. supervised the study and wrote the manuscript with X.H. and B.L. All co-authors contributed to manuscript preparation and research progress discussion.
xsliu@mail.dfci.harvard.edu; bo.li@utsouthwestern.edu; jliu@stat.harvard.edu
Author contributions
ORCID 0000-0002-4450-7239
0000-0002-3517-6351
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SSID ssj0014408
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Snippet Tumor-infiltrating B cells are an important component in the microenvironment but have unclear anti-tumor effects. We enhanced our previous computational...
Tumor-infiltrating B cells are an important component in the microenvironment with unclear anti-tumor impacts. We enhanced our previous computational algorithm...
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proquest
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pubmed
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Publisher
StartPage 560
SubjectTerms 45/91
631/114/2164
631/114/794
631/250/580
631/67/327
631/67/580
Agriculture
Algorithms
Analysis
Animal Genetics and Genomics
Antibodies
Antibody-dependent cell-mediated cytotoxicity
Anticancer properties
Antigens
B cells
B-Lymphocytes - immunology
Base Sequence
Bioinformatics
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer
Cancer genetics
Cancer Research
Care and treatment
Cloning
Complementarity
Complementarity Determining Regions - immunology
Complementarity-determining region
Complementarity-determining region 3
Computer applications
Copy number
Cytotoxicity
Gene Function
Gene sequencing
Genes
Genomes
Genomics
Heavy chains
Human Genetics
Humans
Immune evasion
Immune Evasion - immunology
Immunity
Immunity (Disease)
Immunoglobulin G
Immunoglobulin G - immunology
Immunoglobulin Heavy Chains - immunology
Immunoglobulin Variable Region - immunology
Immunoglobulins
Immunotherapy
Ligands
Lymphocytes B
Major histocompatibility complex
Medical schools
Mutation
Neoplasms - immunology
Novels
Performance evaluation
Ribonucleic acid
Risk factors
RNA
RNA sequencing
Sequence Analysis, RNA - methods
Somatic Hypermutation, Immunoglobulin - immunology
Toxicity
Tumors
Title Landscape of B cell immunity and related immune evasion in human cancers
URI https://link.springer.com/article/10.1038/s41588-018-0339-x
https://www.ncbi.nlm.nih.gov/pubmed/30742113
https://www.proquest.com/docview/2188533257
https://www.proquest.com/docview/2187534950
https://pubmed.ncbi.nlm.nih.gov/PMC6773274
Volume 51
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