Nature genetics · 2019
Landscape of B cell immunity and related immune evasion in human cancers.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.