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

Xihao Hu, Jian Zhang, Jin Wang, Jingxin Fu, Taiwen Li, Xiaoqi Zheng, Binbin Wang, Shengqing Gu, Peng Jiang, Jingyu Fan, Xiaomin Ying, Jing Zhang, Michael C. Carroll, Kai W. Wucherpfennig, Nir Hacohen, Fan Zhang, Peng Zhang, Jun S. Liu, Bo Li, X. Shirley Liu

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)560-567
Number of pages8
JournalNature genetics
Volume51
Issue number3
DOIs
StatePublished - Mar 1 2019

ASJC Scopus subject areas

  • Genetics

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  • Cite this

    Hu, X., Zhang, J., Wang, J., Fu, J., Li, T., Zheng, X., Wang, B., Gu, S., Jiang, P., Fan, J., Ying, X., Zhang, J., Carroll, M. C., Wucherpfennig, K. W., Hacohen, N., Zhang, F., Zhang, P., Liu, J. S., Li, B., & Liu, X. S. (2019). Landscape of B cell immunity and related immune evasion in human cancers. Nature genetics, 51(3), 560-567. https://doi.org/10.1038/s41588-018-0339-x