Single-cell epigenomic profiling of H3K27ac reveals the dynamic changes of B cell driving inflammation-cancer transition

Chen-Yu Wang; Qi-Xin Hu; Jian Chen; Jing-Jing Chen; Zhou Ye; Huan Li; Feng Jin; Lu Jiang; Lian-Yun Li; Ming-Kai Chen; Min Wu

doi:10.59717/j.xinn-oncol.2026.100037

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Single-cell epigenomic profiling of H3K27ac reveals the dynamic changes of B cell driving inflammation-cancer transition

1.
State Key Laboratory of Metabolism and Regulation in Complex Organisms, Frontier Science Center for Immunology and Metabolism, Hubei Key Laboratory of Cell Homeostasis, Hubei Key Laboratory of Developmentally Originated Disease, College of Life Sciences, Taikang Center for Life and Medical Sciences, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430072, China
2.
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, China
3.
These authors contributed equally

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Corresponding authors: wumin@whu.edu.cn (M.W.); lilianyun@whu.edu.cn (L.-Y.L.); kaimingchen@163.com (M.-K.C.)
Received Date: June 05, 2026

Accepted Date: September 22, 2026

Published Online: September 24, 2026

The Innovation Oncology https://doi.org/10.59717/j.xinn-oncol.2026.100037 | Cite this article

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Single-cell profiling mapped cell states and regulatory changes in inflammation-driven colorectal cancer.
  
  Leucine-rich repeat kinase 2 (LRRK2)⁺ B cells emerged during inflammation and suppressed T-cell function.
  
  Epigenetic priming of NF-κB target genes in Lrrk2⁺ B cells drives the inflammation-to-cancer transition.
  
  LRRK2 inhibition reduced LRRK2⁺ B cells and tumor growth, revealing a targetable immune-suppressive axis.

ABSTRACT

ABSTRACT

Transcriptomic and epigenomic analyses at the single-cell level are critical for demonstrating the composition and regulatory network within the tumor microenvironment. Though single-cell ATAC-seq is widely-used, it is insufficient to fully interpret the functional connections. Here, we performed scRNA-seq and H3K27ac MobiChIP profiling in an AOM/DSS-induced colorectal cancer model, and developed an AI-assisted workflow for single-cell epigenomic and transcriptomic integrative analyses. Our results reveal Lrrk2⁺ B cells, one new subset of naïve B cells, are enriched during inflammation and suppresses CD4+/CD8+ T cell function via IL-7/IL-12. Epigenetic priming in Lrrk2⁺ B cells at the inflammation stage enables activation of NF-κB target genes at the cancer stage, driving inflammation-to-cancer transition. Pharmacological LRRK2 inhibition abrogated Lrrk2⁺ B cells and attenuated tumorigenesis. Our study established an integrative strategy enabling high confidence cell identity assignment in sparse epigenomic data, and revealed the roles of B cell subtypes in the regulation of tumor immunity.
- Single-cell sequencing /
- H3K27ac /
- Colorectal cancer /
- B cell /
- Tumor microenvironment

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Wang C.-Y., Hu Q.-X., Chen J., et al. (2026). Single-cell epigenomic profiling of H3K27ac reveals the dynamic changes of B cell driving inflammation-cancer transition. The Innovation Oncology 1:100037. https://doi.org/10.59717/j.xinn-oncol.2026.100037

Wang C.-Y., Hu Q.-X., Chen J., et al. (2026). Single-cell epigenomic profiling of H3K27ac reveals the dynamic changes of B cell driving inflammation-cancer transition. The Innovation Oncology 1:100037. https://doi.org/10.59717/j.xinn-oncol.2026.100037

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Single-cell epigenomic profiling of H3K27ac reveals the dynamic changes of B cell driving inflammation-cancer transition

GRAPHICAL ABSTRACT

PUBLIC SUMMARY

ABSTRACT