Tumor-infiltrating B cell is an important component in the microenvironment with unclear antitumor impacts. We enhanced our previous computational algorithm TRUST to extract the B cell immunoglobulin (Ig) hypervariable regions from bulk tumor RNA-seq data. TRUST assembled over 30 million complementarity-determining region 3 (CDR3s) of the B-cell heavy chain (IgH) from The Cancer Genome Atlas (TCGA). Widespread B-cell clonal expansions and Ig subclass switch events were observed in diverse human cancers. Prevalent somatic copy number alterations (SCNA) in MICA/B genes related to antibody-dependent cell mediated cytotoxicity (ADCC) were identified in tumors with elevated B-cell activity. IgG3-1 subclass switch interacts with the B cell receptor affinity maturation and defects in the ADCC pathway. The comprehensive pan-cancer analyses of tumor-infiltrating B-cell receptor repertoires revealed novel tumor immune evasion mechanism through genetic alterations. The IgH sequences identified in this work are potentially useful resources for future development of immunotherapies.

Citation Format: Xihao Sherlock Hu, Jian Zhang, Jun Liu, Bo Li, Xiaole Shirley Liu. Landscape of B-cell immunity and related immune evasion in human cancers [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B92.