To study the role of tumor-infiltrating B cells, Hu and Zhang et al. modified the TRUST algorithm to assemble over 30 million CDR3 sequences of the B cell receptor immunoglobulin heavy chain using bulk tumor RNAseq data from TCGA, spanning 32 cancer types. The researchers observed widespread B cell clonal expansion within tumors and identified a relationship between the clonal expansion of B cells with IgG3-1 class switches and survival in patients with high somatic hypermutation rates. They also identified possible evidence of elevated ADCC and activation of tumor escape mechanisms coinciding with B cell response.
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.
Author Info: (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 Institut
Author Info: (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) Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA. Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. (4) Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA. Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. (5) State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. (6) Department of Mathematics, Shanghai Normal University, Shanghai, China. (7) Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA. Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. (8) Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA. (9) Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA. (10) Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA. Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. (11) Center for Computational Biology, Beijing Institute of Basic Medical Sciences, Beijing, China. (12) Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. (13) Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. (14) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. (15) Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. (16) Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. (17) Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. (18) Department of Statistics, Harvard University, Cambridge, MA, USA. jliu@stat.harvard.edu. (19) Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA. bo.li@utsouthwestern.edu. (20) Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA. xsliu@jimmy.harvard.edu. 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. Department of Statistics, Harvard University, Cambridge, MA, USA. xsliu@jimmy.harvard.edu.
