Journal of Shanghai Jiao Tong University (Medical Science) >

2022 , Vol. 42 >Issue 4: 472 - 481

DOI: https://doi.org/10.3969/j.issn.1674-8115.2022.04.009

Basic research

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

  • Qiyu GONG ,
  • Lei CHEN
Expand
  • Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
CHEN Lei, E-mail: lei.chen@sjtu.edu.cn.

Received date: 2021-11-18

  Accepted date: 2022-03-28

  Online published: 2022-04-28

Fold

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

Cite this article

Qiyu GONG , Lei CHEN . 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 . DOI: 10.3969/j.issn.1674-8115.2022.04.009

References

1 XIE Y H, CHEN Y X, FANG J Y. Comprehensive review of targeted therapy for colorectal cancer[J]. Signal Transduct Target Ther, 2020, 5(1):22.
2 BINNEWIES M, ROBERTS E W, KERSTEN K, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy[J]. Nat Med, 2018, 24(5):541-550.
3 CIARDIELLO D, VITIELLO P P, CARDONE C, et al. Immunotherapy of colorectal cancer: challenges for therapeutic efficacy[J]. Cancer Treat Rev, 2019, 76: 22-32.
4 ZHAO P, LI L, JIANG X, et al. Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy[J]. J Hematol Oncol, 2019, 12(1): 54.
5 GALON J, COSTES A, SANCHEZ-CABO F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome[J]. Science, 2006, 313(5795): 1960-1964.
6 GARBER K. Driving T-cell immunotherapy to solid tumors[J]. Nat Biotechnol, 2018, 36(3): 215-219.
7 SHEN P, FILLATREAU S. Antibody-independent functions of B cells: a focus on cytokines[J]. Nat Rev Immunol, 2015, 15(7):441-451.
8 SCHARER C D, PATTERSON D G, MI T, et al. Antibody-secreting cell destiny emerges during the initial stages of B-cell activation[J]. Nat Commun, 2020, 11(1): 3989.
9 GUNDERSON A J, COUSSENS L M. B cells and their mediators as targets for therapy in solid tumors[J]. Exp Cell Res, 2013, 319(11):1644-1649.
10 SHARONOV G V, SEREBROVSKAYA E O, YUZHAKOVA D V, et al. B cells, plasma cells and antibody repertoires in the tumour microenvironment[J]. Nat Rev Immunol, 2020, 20(5): 294-307.
11 BERGOMAS F, GRIZZI F, DONI A, et al. Tertiary intratumor lymphoid tissue in colo-rectal cancer[J]. Cancers (Basel), 2011, 4(1):1-10.
12 SAUTèS-FRIDMAN C, PETITPREZ F, CALDERARO J, et al. Tertiary lymphoid structures in the era of cancer immunotherapy[J]. Nat Rev Cancer, 2019, 19(6): 307-325.
13 SCHULTZE J L, MICHALAK S, SEAMON M J, et al. CD40-activated human B cells: an alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy[J]. J Clin Invest, 1997, 100(11):2757-2765.
14 ZHANG W, FENG Q, WANG C, et al. Characterization of the B cell receptor repertoire in the intestinal mucosa and of tumor-infiltrating lymphocytes in colorectal adenoma and carcinoma[J]. J Immunol, 2017, 198(9): 3719-3728.
15 SCHOORL R, RIVIERE A B, BORNE A E, et al. Identification of T and B lymphocytes in human breast cancer with immunohistochemical techniques[J]. Am J Pathol, 1976, 84(3):529-544.
16 POSCH F, SILINA K, LEIBL S, et al. Maturation of tertiary lymphoid structures and recurrence of stage Ⅱ and Ⅲ colorectal cancer[J]. Oncoimmunology, 2018, 7(2): e1378844.
17 ZHANG L, LI Z, SKRZYPCZYNSKA K M, et al. Single-cell analyses inform mechanisms of myeloid-targeted therapies in colon cancer[J]. Cell, 2020, 181(2): 442-459.e29.
18 WANG J, XU Y, CHEN Z, et al. Liver immune profiling reveals pathogenesis and therapeutics for biliary atresia[J]. Cell, 2020, 183(7):1867-1883.e26.
19 KROEGER D R, MILNE K, NELSON B H. Tumor-infiltrating plasma cells are associated with tertiary lymphoid structures, cytolytic T-cell responses, and superior prognosis in ovarian cancer[J]. Clin Cancer Res, 2016, 22(12): 3005-3015.
20 LUND F E, RANDALL T D. Effector and regulatory B cells: modulators of CD4+ T cell immunity[J]. Nat Rev Immunol, 2010, 10(4): 236-247.
21 NIELSEN J S, SAHOTA R A, MILNE K, et al. CD20+ tumor-infiltrating lymphocytes have an atypical CD27- memory phenotype and together with CD8+ T cells promote favorable prognosis in ovarian cancer[J]. Clin Cancer Res, 2012, 18(12): 3281-3292.
22 RIVERA A, CHEN C C, RON N, et al. Role of B cells as antigen-presenting cells in vivo revisited: antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations[J]. Int Immunol, 2001, 13(12): 1583-1593.
Options
Outlines

/

〈 〉