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Nat Genet. 2019 Mar;51(3):560-567. doi: 10.1038/s41588-018-0339-x. Epub 2019 Feb 11.

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

Author information

1
Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA.
2
Center for Computational Biology, Beijing Institute of Basic Medical Sciences, Beijing, China.
3
Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
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.
6
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
7
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
8
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
9
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
10
Department of Statistics, Harvard University, Cambridge, MA, USA. jliu@stat.harvard.edu.
11
Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA. bo.li@utsouthwestern.edu.
12
Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA. xsliu@jimmy.harvard.edu.
13
Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. xsliu@jimmy.harvard.edu.
14
Department of Statistics, Harvard University, Cambridge, MA, USA. xsliu@jimmy.harvard.edu.

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.

PMID:
30742113
PMCID:
PMC6773274
DOI:
10.1038/s41588-018-0339-x
[Indexed for MEDLINE]
Free PMC Article

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