DataVXAdvanced SciencePaper
journal article·2026-02Open access

The KDM6B/SLC10A2 Axis Suppresses MDSCs Recruitment via ERK/AP‐1 Signaling in Colorectal Cancer

Zhibo Hu, Jing Xun, Bin Liu, Xiaolin Jiang, Yingdi Han, Huichao Yang, Qi Gao, Ruifang Gao, Aimin Zhang, Xueliang Wu, Dapeng Zhang, Dihua Li, Tian Li, Shimin Yang, Ximo Wang, Xiangyang Yu, Qi Zhang

Advanced Science· Volume 13· Issue 9
Publisher pageOpen full text
Source abstract

Abstract

Abstract Colorectal cancer (CRC) progression is regulated by an immunosuppressive tumor microenvironment, but the epigenetic mechanisms governing this milieu remain unclear. This study identifies the histone demethylase KDM6B as a key regulator of myeloid‐derived suppressor cells (MDSCs) recruitment in CRC. Intestinal epithelial‐specific KDM6B deletion promotes tumor growth by increasing MDSCs‐mediated immunosuppression. Mechanistically, KDM6B directly transcriptionally activates solute carrier family 10 member 2 (SLC10A2), whereas its loss increased H3K27me3 repression at the SLC10A2 promoter, activating the ERK/AP‐1 pathway and subsequent CXCL/CXCR2‐dependent MDSC recruitment. Clinically, KDM6B expression positively correlated with SLC10A2 levels and inversely correlated with MDSC infiltration in human CRC specimens. More importantly, KDM6B knockdown conferred resistance to anti‐PD‐1 therapy in CRC, whereas its overexpression synergized with anti‐PD‐1 therapy. In conclusion, this study establishes the KDM6B–SLC10A2 axis as a novel epigenetic immune checkpoint, highlighting its potential as a therapeutic target for reprogramming the immunosuppressive microenvironment in CRC.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Immune cells in cancer · Neutrophil, Myeloperoxidase and Oxidative Mechanisms · Immune responses and vaccinations

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Tianjin Nankai Hospital Tianjin Medical University; Institute of Integrative Medicine for Acute Abdominal Diseases Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair Tianjin 300100 China

Tianjin Institute of Medical and Pharmaceutical Sciences Tianjin 300020 China

Tianjin Nankai Hospital Tianjin Medical University Tianjin 300100 China

The First Affiliated Hospital of Hebei North University Hebei 075000 China

Tianjin Medical University Institute of Integrative Medicine for Acute Abdominal Diseases Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair Tianjin 300100 China

Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Tianjin Key Laboratory of Digestive Cancer Tianjin's Clinical Research Center for Cancer Tianjin 300060 China

Funding

National Key Research and Development Program of China · Tianjin Municipal Health Commission

References (31)

Show source-provided references
1. 10.1001/jama.2021.010610.1001/jama.2021.0106 ↗
2. 10.1200/JCO.2017.76.990110.1200/JCO.2017.76.9901 ↗
3. 10.1038/s41573-020-0077-510.1038/s41573-020-0077-5 ↗
4. 10.1038/s41575-024-00934-z10.1038/s41575-024-00934-z ↗
5. 10.1126/sciadv.adh270810.1126/sciadv.adh2708 ↗
6. 10.1038/s43018-023-00620-010.1038/s43018-023-00620-0 ↗
7. 10.1016/j.canlet.2025.21793910.1016/j.canlet.2025.217939 ↗
8. 10.1038/s43018-023-00620-010.1038/s43018-023-00620-0 ↗
9. 10.1038/s41571-023-00846-y10.1038/s41571-023-00846-y ↗
10. 10.1016/j.ccell.2023.02.00910.1016/j.ccell.2023.02.009 ↗
11. 10.1038/s41568-022-00546-210.1038/s41568-022-00546-2 ↗
12. 10.1038/s41568-023-00635-w10.1038/s41568-023-00635-w ↗
13. 10.1038/s41571-023-00846-y10.1038/s41571-023-00846-y ↗
14. 10.1158/0008-5472.CAN-15-316410.1158/0008-5472.CAN-15-3164 ↗
15. 10.1016/j.intimp.2023.10983910.1016/j.intimp.2023.109839 ↗
16. 10.1186/s12943-022-01657-y10.1186/s12943-022-01657-y ↗
17. 10.1038/s41586-024-08257-410.1038/s41586-024-08257-4 ↗
18. 10.1158/2159-8290.CD-23-076210.1158/2159-8290.CD-23-0762 ↗
19. 10.1016/j.ccell.2023.08.01210.1016/j.ccell.2023.08.012 ↗
20. 10.1186/s12943-023-01830-x10.1186/s12943-023-01830-x ↗
21. 10.1038/s41467-024-47096-910.1038/s41467-024-47096-9 ↗
22. 10.1186/s12943-025-02249-210.1186/s12943-025-02249-2 ↗
23. 10.1038/s43018-021-00258-w10.1038/s43018-021-00258-w ↗
24. 10.1002/cac2.1229510.1002/cac2.12295 ↗
25. 10.1038/s41571-023-00846-y10.1038/s41571-023-00846-y ↗
26. 10.1016/j.biopha.2020.11083510.1016/j.biopha.2020.110835 ↗
27. 10.7150/ijms.4581310.7150/ijms.45813 ↗
28. 10.1136/gutjnl-2024-33442510.1136/gutjnl-2024-334425 ↗
29. 10.1038/s41401-018-0195-310.1038/s41401-018-0195-3 ↗
30. 10.1038/s41467-022-28772-010.1038/s41467-022-28772-0 ↗
31. 10.1016/j.ccell.2019.02.00810.1016/j.ccell.2019.02.008 ↗