Abstract
Tumor-infiltrating B cells can play an important role in anti-tumor responses but their presence is not well understood. In this study, we extracted the B cell receptor repertoires from 9522 tumor and adjacent non-tumor samples across 28 tumor types in the Cancer Genome Atlas project and performed diversity and network analysis. We identified differences in diversity and network statistics across tumor types and subtypes and observed a trend towards increased clonality in primary tumors compared to adjacent non-tumor tissues. We also found significant associations between the repertoire features and mutation load, tumor stage, and age. Our V-gene usage analysis identified similar V-gene usage patterns in colorectal and endometrial cancers. Lastly, we evaluated the prognostic value of the repertoire features and identified significant associations with survival in seven tumor types. This study warrants further research into better understanding the role of tumor-infiltrating B cells across a wide range of tumor types.
Highlights
While B cells are well-established as an integral part of the adaptive immune system, only recently studies began to elucidate their role in cancer [1, 2]
We analyzed the B cell repertoires across the The Cancer Genome Atlas (TCGA) tumor samples corresponding to 28 tumor types with a total of 8854 tumor and 688 adjacent non-tumor samples (Figure 1A and Supplementary Table 1)
Many of the tumor types that have the highest IGH, IGK, and IGL expression such as lung squamous cell carcinoma (LUAD), lung adenocarcinoma (LUAD), head and neck squamous cell carcinoma (HNSC), and skin cutaneous melanoma (SKCM) (Figure 1B), are the tumor types that have mutational burden as well as high leukocyte fractions (Supplementary Figure 1C), which was estimated by Thorsson et al using methylation data [7], and are most responsive to checkpoint inhibitors [7]
Summary
While B cells are well-established as an integral part of the adaptive immune system, only recently studies began to elucidate their role in cancer [1, 2]. A main function of B cells is to recognize specific antigens with the immunoglobulins (Ig), or B cell receptors (BCR), on their cell surface. These Ig are made up of two heavy chains (IGH) and two light chains, the kappa (k) chains (IGK) or the lambda (l) chains (IGL). Ig are generated through a process called somatic recombination where variable (V), diversity (D), and joining (J) gene segments are randomly combined to create a diverse collection of antigen receptors which can recognize a wide range of antigens. B cells undergo a process called somatic hypermutation (SHM) upon antigen binding which introduces additional mutations into the variable regions of the Ig genes, further diversifying the receptors
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