Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer
Abstract Background Triple-negative breast cancer (TNBC) development may be associated with tumor immune escape. This study explores whether the CHI3L1/MAF/CTLA4/S100A4 axis affects immune escape in TNBC through interplay with triple-negative breast cancer stem cells (TN-BCSCs). Objective The aim of...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04532-6 |
| _version_ | 1797451673267863552 |
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| author | Shufeng Ji Hao Yu Dan Zhou Xulong Fan Yan Duan Yijiang Tan Min Lang Guoli Shao |
| author_facet | Shufeng Ji Hao Yu Dan Zhou Xulong Fan Yan Duan Yijiang Tan Min Lang Guoli Shao |
| author_sort | Shufeng Ji |
| collection | DOAJ |
| description | Abstract Background Triple-negative breast cancer (TNBC) development may be associated with tumor immune escape. This study explores whether the CHI3L1/MAF/CTLA4/S100A4 axis affects immune escape in TNBC through interplay with triple-negative breast cancer stem cells (TN-BCSCs). Objective The aim of this study is to utilize single-cell transcriptome sequencing (scRNA-seq) to uncover the molecular mechanisms by which the CHI3L1/MAF/CTLA4 signaling pathway may mediate immune evasion in triple-negative breast cancer through the interaction between tumor stem cells (CSCs) and immune cells. Methods Cell subsets in TNBC tissues were obtained through scRNA-seq, followed by screening differentially expressed genes in TN-BCSCs and B.C.s (CD44+ and CD24−) and predicting the transcription factor regulated by CHI3L1. Effect of CHI3L1 on the stemness phenotype of TNBC cells investigated. Effects of BCSCs-231-derived CHI3L1 on CTLA4 expression in T cells were explored after co-culture of BCSCs-231 cells obtained from microsphere culture of TN-BCSCs with T cells. BCSCs-231-treated T cells were co-cultured with CD8+ T cells to explore the resultant effect on T cell cytotoxicity. An orthotopic B.C. transplanted tumor model in mice with humanized immune systems was constructed, in which the Role of CHI3L1/MAF/CTLA4 in the immune escape of TNBC was explored. Results Eight cell subsets were found in the TNBC tissues, and the existence of TN-BCSCs was observed in the epithelial cell subset. CHI3L1 was related to the stemness phenotype of TNBC cells. TN-BCSC-derived CHI3L1 increased CTLA4 expression in T cells through MAF, inhibiting CD8+ T cell cytotoxicity and inducing immunosuppression. Furthermore, the CTLA4+ T cells might secrete S100A4 to promote the stemness phenotype of TNBC cells. Conclusions TN-BCSC-derived CHI3L1 upregulates CTLA4 expression in T cells through MAF, suppressing the function of CD8+ T cells, which promotes the immune escape of TNBC. |
| first_indexed | 2024-03-09T14:57:53Z |
| format | Article |
| id | doaj.art-2ebcb74a6d124385881e9d0217925ccb |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-09T14:57:53Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-2ebcb74a6d124385881e9d0217925ccb2023-11-26T14:05:11ZengBMCJournal of Translational Medicine1479-58762023-10-0121111810.1186/s12967-023-04532-6Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancerShufeng Ji0Hao Yu1Dan Zhou2Xulong Fan3Yan Duan4Yijiang Tan5Min Lang6Guoli Shao7Special Medical Service Center, General Surgery, Zhujiang Hospital of Southern Medical UniversitySpecial Medical Service Center, General Surgery, Zhujiang Hospital of Southern Medical UniversityDepartment of Breast Surgery, The First People’s Hospital of FoshanDepartment of Breast Surgery, Maternity and Children’s Healthcare Hospital of FoshanSpecial Medical Service Center, General Surgery, Zhujiang Hospital of Southern Medical UniversitySpecial Medical Service Center, General Surgery, Zhujiang Hospital of Southern Medical UniversitySpecial Medical Service Center, General Surgery, Zhujiang Hospital of Southern Medical UniversitySpecial Medical Service Center, General Surgery, Zhujiang Hospital of Southern Medical UniversityAbstract Background Triple-negative breast cancer (TNBC) development may be associated with tumor immune escape. This study explores whether the CHI3L1/MAF/CTLA4/S100A4 axis affects immune escape in TNBC through interplay with triple-negative breast cancer stem cells (TN-BCSCs). Objective The aim of this study is to utilize single-cell transcriptome sequencing (scRNA-seq) to uncover the molecular mechanisms by which the CHI3L1/MAF/CTLA4 signaling pathway may mediate immune evasion in triple-negative breast cancer through the interaction between tumor stem cells (CSCs) and immune cells. Methods Cell subsets in TNBC tissues were obtained through scRNA-seq, followed by screening differentially expressed genes in TN-BCSCs and B.C.s (CD44+ and CD24−) and predicting the transcription factor regulated by CHI3L1. Effect of CHI3L1 on the stemness phenotype of TNBC cells investigated. Effects of BCSCs-231-derived CHI3L1 on CTLA4 expression in T cells were explored after co-culture of BCSCs-231 cells obtained from microsphere culture of TN-BCSCs with T cells. BCSCs-231-treated T cells were co-cultured with CD8+ T cells to explore the resultant effect on T cell cytotoxicity. An orthotopic B.C. transplanted tumor model in mice with humanized immune systems was constructed, in which the Role of CHI3L1/MAF/CTLA4 in the immune escape of TNBC was explored. Results Eight cell subsets were found in the TNBC tissues, and the existence of TN-BCSCs was observed in the epithelial cell subset. CHI3L1 was related to the stemness phenotype of TNBC cells. TN-BCSC-derived CHI3L1 increased CTLA4 expression in T cells through MAF, inhibiting CD8+ T cell cytotoxicity and inducing immunosuppression. Furthermore, the CTLA4+ T cells might secrete S100A4 to promote the stemness phenotype of TNBC cells. Conclusions TN-BCSC-derived CHI3L1 upregulates CTLA4 expression in T cells through MAF, suppressing the function of CD8+ T cells, which promotes the immune escape of TNBC.https://doi.org/10.1186/s12967-023-04532-6CHI3L1CTLA4MAFS100A4Triple-negative breast cancerCancer stem cells |
| spellingShingle | Shufeng Ji Hao Yu Dan Zhou Xulong Fan Yan Duan Yijiang Tan Min Lang Guoli Shao Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer Journal of Translational Medicine CHI3L1 CTLA4 MAF S100A4 Triple-negative breast cancer Cancer stem cells |
| title | Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer |
| title_full | Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer |
| title_fullStr | Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer |
| title_full_unstemmed | Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer |
| title_short | Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer |
| title_sort | cancer stem cell derived chi3l1 activates the maf ctla4 signaling pathway to promote immune escape in triple negative breast cancer |
| topic | CHI3L1 CTLA4 MAF S100A4 Triple-negative breast cancer Cancer stem cells |
| url | https://doi.org/10.1186/s12967-023-04532-6 |
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