Citation:
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, and X. Shirley Liu. 2019. “
Landscape of B cell immunity and related immune evasion in human cancers.” Nat Genet, 51, 3, Pp. 560-567.
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.