Role of circulating and infiltrating B cells in immune microenvironment of colorectal cancer by multi-omics data profiling

doi:10.3969/j.issn.1674-8115.2022.04.009

Abstract

Abstract: Objective

·To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of colorectal cancer and discover the potential molecular-driving mechanisms behind the above transformation. Then to analyze the interaction patterns between B cell subsets and other immune cells in the microenvironment, including the function analysis of communicating molecules. All these steps assist to find possible regulatory ways to augment the anti-tumor effect of B cells.

Methods

·Paired tumor, normal and peripheral blood tissues were collected from three patients with colorectal cancer. A total of 9 samples were applied to prepare the single-cell suspension. Then all immune cells were sorted by flow cytometry. 10X Genomics platform was applied for single-cell transcriptome and B cell receptor repertoire (BCR) sequencing. Bioinformatic tools such as Seurat etc. were taken to analyze scRNA and BCR data. The downstream analysis includes differential analysis of B cell in tumor versus normal tissues, cell interaction analysis in the immune microenvironment and regulatory networks of B cell subsets.

Results

·CD20⁺B cells were significantly increased in tumor versus normal tissues, especially germinal center B cells (GCB), which showed positively clonal amplification and high mutation level. Besides, GCB showed the tendency of transformation into memory B cells. On the contrary, plasma cells significantly reduced their activity in tumor, which was dominated by the IgA class. In addition, comparing with the immune microenvironment in normal tissues, GCB in tumor tissues are more closely connected with T cells and other immune cells, and the communication molecule pairs that positively regulate immune function were significantly enriched.

Conclusion

·The importance of GCB in the immune microenvironment of colorectal cancer is greatly increased. And they exert a positive anti-tumor effect through the up-regulated heavy-chain mutation level and their close association with surrounding immune cells.

Key words: bioinformatics, single cell sequencing, colorectal cancer, immunology, B cell

CLC Number:

R735.3

GONG Qiyu, CHEN Lei. Role of circulating and infiltrating B cells in immune microenvironment of colorectal cancer by multi-omics data profiling[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(4): 472-481.

Figures/Tables 6

Fig 1 Transcriptome map of main immune cells

Fig 2 Atlas of B cell subclusters in CRC

Fig 3 Composition of B cell subsets in tumor and normal tissues by TCGA-COAD data profiling

Fig 4 Interecting pairs between B cell subsets with T cells and myeloid cells

Fig 5 Clonal expansion index of B cell subsets and mutation level of GCB

Fig 6 Transition index of B cell subsets among normal (A), tunor (B) and PBCM (C) sample

TrendMD

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