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

被引：125

作者：

Hu, Xihao ^{[1
,2
]}

Zhan, Jian ^{[3
]}

Wang, Jin ^{[1
,2
,4
]}

Fu, Jingxin ^{[1
,2
,4
]}

Li, Taiwen ^{[5
]}

Zheng, Xiaoqi ^{[6
]}

Wang, Binbin ^{[1
,2
,4
]}

Gu, Shengqing ^{[1
,2
]}

Jiang, Peng ^{[1
,2
]}

Fan, Jingyu ^{[1
,2
,4
]}

Ying, Xiaomin ^{[3
]}

Zhang, Jing ^{[4
]}

Carroll, Michael C. ^{[7
]}

Wucherpfennig, Kai W. ^{[8
]}

Hacohen, Nir ^{[9
]}

Zhang, Fan ^{[4
,10
]}

Zhang, Peng ^{[4
,10
]}

Liu, Jun S. ^{[11
]}

Li, Bo ^{[12
]}

Liu, X. Shirley ^{[1
,2
,4
,11
]}

机构：

[1] Dana Farber Canc Inst, Dept Data Sci, Boston, MA 02115 USA

[2] Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA

[3] Beijing Inst Basic Med Sci, Ctr Computat Biol, Beijing, Peoples R China

[4] Tongji Univ, Shanghai Key Lab TB, Clin Translat Res Ctr, Shanghai Pulm Hosp,Sch Life Sci & Technol, Shanghai, Peoples R China

[5] Sichuan Univ, State Key Lab Oral Dis, West China Hosp Stomatol, Chengdu, Sichuan, Peoples R China

[6] Shanghai Normal Univ, Dept Math, Shanghai, Peoples R China

[7] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA

[8] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA

[9] Harvard Med Sch, Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02115 USA

[10] Tongji Univ, Shanghai Pulm Hosp, Dept Thorac Surg, Sch Med, Shanghai, Peoples R China

[11] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA

[12] Univ Texas Southwestern Med Ctr Dallas, Lyda Hill Dept Bioinformat, Dallas, TX 75390 USA

来源：

NATURE GENETICS | 2019年 / 51卷 / 03期

基金：

中国国家自然科学基金;

关键词：

FC-GAMMA RECEPTORS; SOMATIC HYPERMUTATION; SEQUENCING DATA; LYMPHOCYTES; GENERATION; MUTATIONS; SUPPRESSION; REPERTOIRES; DIVERSITY; RESPONSES;

D O I：

10.1038/s41588-018-0339-x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：560 / +

页数：10

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