BCL9 regulates CD226 and CD96 checkpoints in CD8(+) T cells to improve PD-1 response in cancer
文献类型：期刊论文
| 作者 | Feng, Mei1,2; Wu, Zhongen2; Zhou, Yan3; Wei, Zhuang4; Tian, Enming2; Mei, Shenglin5; Zhu, Yuanyuan2; Liu, Chenglong2; He, Fenglian2; Li, Huiyu2 |
| 刊名 | SIGNAL TRANSDUCTION AND TARGETED THERAPY
 |
| 出版日期 | 2021-08-20 |
| 卷号 | 6期号:1页码:14 |
| ISSN号 | 2095-9907 |
| DOI | 10.1038/s41392-021-00730-0 |
| 通讯作者 | Lambrechts, Diether(diether.lambrechts@kuleuven.be) ; Wang, Ming-Wei(mwwang@simm.ac.cn) ; Zhu, Di(zhudi@fudan.edu.cn) |
| 英文摘要 | To date, the overall response rate of PD-1 blockade remains unsatisfactory, partially due to limited understanding of tumor immune microenvironment (TIME). B-cell lymphoma 9 (BCL9), a key transcription co-activator of the Wnt pathway, is highly expressed in cancers. By genetic depletion and pharmacological inhibition of BCL9 in tumors, we found that BCL9 suppression reduced tumor growth, promoted CD8(+) T cell tumor infiltration, and enhanced response to anti-PD-1 treatment in mouse colon cancer models. To determine the underlying mechanism of BCL9's role in TIME regulation, single-cell RNA-seq was applied to reveal cellular landscape and transcription differences in the tumor immune microenvironment upon BCL9 inhibition. CD155-CD226 and CD155-CD96 checkpoints play key roles in cancer cell/CD8(+) T cell interaction. BCL9 suppression induces phosphorylation of VAV1 in CD8(+) T cells and increases GLI1 and PATCH expression to promote CD155 expression in cancer cells. In The Cancer Genome Atlas database analysis, we found that BCL9 expression is positively associated with CD155 and negatively associated with CD226 expression. BCL9 is also linked to adenomatous polyposis coli (APC) mutation involved in patient survival following anti-PD-1 treatment. This study points to cellular diversity within the tumor immune microenvironment affected by BCL9 inhibition and provides new insights into the role of BCL9 in regulating CD226 and CD96 checkpoints |
| WOS关键词 | COLORECTAL-CANCER ; DNAM-1 ; ANTITUMOR ; TUMORS ; INHIBITION ; ACTIVATION ; EXPRESSION ; MOLECULE ; ADHESION ; IMMUNITY |
| 资助项目 | National Natural Science Foundation of China[81872895] ; National Natural Science Foundation of China[82073881] ; National Natural Science Foundation of China[81872915] ; National Natural Science Foundation of China[82073904] ; National Natural Science Foundation of China[82011530150] ; Shanghai Municipal Education Commission (Shanghai Top-Level University Capacity Building Program)[DGF817029-04] ; Shanghai Science and Technology Commission[18ZR1403900] ; Shanghai Science and Technology Commission[20430713600] ; Shanghai Science and Technology Commission[18JC1413800] ; Fudan-SIMM Joint Research Fund[FU-SIMM20181010] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000687166300002 |
| 出版者 | SPRINGERNATURE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/297993]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Lambrechts, Diether; Wang, Ming-Wei; Zhu, Di |
| 作者单位 | 1.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai, Peoples R China 2.Fudan Univ, Sch Pharm, Shanghai, Peoples R China 3.Chinese Acad Sci, Innovat Ctr Cell Signaling Network, CAS Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol,Key Lab Syst Biol,Shangh, Shanghai, Peoples R China 4.Tongji Univ, Shanghai Pulm Hosp, Clin Translat Res Ctr, Sch Life Sci & Technol, Shanghai, Peoples R China 5.Univ Calif San Francisco, Sch Med, San Francisco, CA USA 6.Zhejiang Univ, Womens Hosp, Dept Gynecol Oncol, Sch Med, Hangzhou, Peoples R China 7.Katholieke Univ Leuven, VIB Ctr Canc Biol, Leuven, Belgium 8.Katholieke Univ Leuven, Lab Translat Genet, Dept Human Genet, Leuven, Belgium 9.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 10.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Feng, Mei,Wu, Zhongen,Zhou, Yan,et al. BCL9 regulates CD226 and CD96 checkpoints in CD8(+) T cells to improve PD-1 response in cancer[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2021,6(1):14. |
| APA | Feng, Mei.,Wu, Zhongen.,Zhou, Yan.,Wei, Zhuang.,Tian, Enming.,...&Zhu, Di.(2021).BCL9 regulates CD226 and CD96 checkpoints in CD8(+) T cells to improve PD-1 response in cancer.SIGNAL TRANSDUCTION AND TARGETED THERAPY,6(1),14. |
| MLA | Feng, Mei,et al."BCL9 regulates CD226 and CD96 checkpoints in CD8(+) T cells to improve PD-1 response in cancer".SIGNAL TRANSDUCTION AND TARGETED THERAPY 6.1(2021):14. |
入库方式： OAI收割
来源：上海药物研究所
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