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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Vydáno v:	Nature genetics Ročník 51; číslo 3; s. 560 - 567
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.03.2019 Nature Publishing Group
Témata:	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 China
ISSN:	1061-4036, 1546-1718, 1546-1718
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/s41588-018-0339-x