Integrated Analysis of Single-Cell and Bulk RNA-Sequencing Reveals a Tissue-Resident Macrophage-Related Signature for Predicting Immunotherapy Response in Breast Cancer Patients
Immune checkpoint therapy (ICT) is among the widely used treatments for breast cancer (BC), but most patients do not respond to ICT and the availability of the predictive biomarkers is limited. Emerging evidence indicates that tissue-resident macrophages (RTMs) inhibit BC progression, suggesting tha...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/22/5506 |
| _version_ | 1797465790383915008 |
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| author | Zi-An Xia You Zhou Jun Li Jiang He |
| author_facet | Zi-An Xia You Zhou Jun Li Jiang He |
| author_sort | Zi-An Xia |
| collection | DOAJ |
| description | Immune checkpoint therapy (ICT) is among the widely used treatments for breast cancer (BC), but most patients do not respond to ICT and the availability of the predictive biomarkers is limited. Emerging evidence indicates that tissue-resident macrophages (RTMs) inhibit BC progression, suggesting that their presence may predict immunotherapy response. A single-cell RNA-sequencing analysis of BC samples was performed to identify five RTM clusters with a mixed phenotype of M1-M2 macrophages. The comprehensive results showed that a high score of each RTM cluster was associated with a high infiltration of CD8+ T cells, M1 macrophages, and dendritic cells, and improved overall survival. In addition, a low score of each RTM cluster was associated with a high infiltration of M0 macrophages, naïve B cells and Tregs, and poor overall survival. Gene signatures from each RTM cluster were significantly enriched in responders compared with nonresponders. Each RTM cluster expression was significantly higher in responders than in nonresponders. The analyses of bulk RNA-seq datasets of BC samples led to identification and validation of a gene expression signature, named RTM.Sig, which contained the related genes of RTM clusters for predicting response to immunotherapy. This study highlights RTM.Sig could provide a valuable tool for clinical decisions in administering ICT. |
| first_indexed | 2024-03-09T18:26:35Z |
| format | Article |
| id | doaj.art-9cb3753263224a3a8b85aacd1a659047 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T18:26:35Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-9cb3753263224a3a8b85aacd1a6590472023-11-24T07:52:18ZengMDPI AGCancers2072-66942022-11-011422550610.3390/cancers14225506Integrated Analysis of Single-Cell and Bulk RNA-Sequencing Reveals a Tissue-Resident Macrophage-Related Signature for Predicting Immunotherapy Response in Breast Cancer PatientsZi-An Xia0You Zhou1Jun Li2Jiang He3Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Pathology, Tongji Medical College Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Nuclear Medicine, Peking University Shenzhen Hospital, Guangdong 518036, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, ChinaImmune checkpoint therapy (ICT) is among the widely used treatments for breast cancer (BC), but most patients do not respond to ICT and the availability of the predictive biomarkers is limited. Emerging evidence indicates that tissue-resident macrophages (RTMs) inhibit BC progression, suggesting that their presence may predict immunotherapy response. A single-cell RNA-sequencing analysis of BC samples was performed to identify five RTM clusters with a mixed phenotype of M1-M2 macrophages. The comprehensive results showed that a high score of each RTM cluster was associated with a high infiltration of CD8+ T cells, M1 macrophages, and dendritic cells, and improved overall survival. In addition, a low score of each RTM cluster was associated with a high infiltration of M0 macrophages, naïve B cells and Tregs, and poor overall survival. Gene signatures from each RTM cluster were significantly enriched in responders compared with nonresponders. Each RTM cluster expression was significantly higher in responders than in nonresponders. The analyses of bulk RNA-seq datasets of BC samples led to identification and validation of a gene expression signature, named RTM.Sig, which contained the related genes of RTM clusters for predicting response to immunotherapy. This study highlights RTM.Sig could provide a valuable tool for clinical decisions in administering ICT.https://www.mdpi.com/2072-6694/14/22/5506breast cancerimmune checkpoint therapytissue-resident macrophagessingle-cell RNA-sequencing |
| spellingShingle | Zi-An Xia You Zhou Jun Li Jiang He Integrated Analysis of Single-Cell and Bulk RNA-Sequencing Reveals a Tissue-Resident Macrophage-Related Signature for Predicting Immunotherapy Response in Breast Cancer Patients Cancers breast cancer immune checkpoint therapy tissue-resident macrophages single-cell RNA-sequencing |
| title | Integrated Analysis of Single-Cell and Bulk RNA-Sequencing Reveals a Tissue-Resident Macrophage-Related Signature for Predicting Immunotherapy Response in Breast Cancer Patients |
| title_full | Integrated Analysis of Single-Cell and Bulk RNA-Sequencing Reveals a Tissue-Resident Macrophage-Related Signature for Predicting Immunotherapy Response in Breast Cancer Patients |
| title_fullStr | Integrated Analysis of Single-Cell and Bulk RNA-Sequencing Reveals a Tissue-Resident Macrophage-Related Signature for Predicting Immunotherapy Response in Breast Cancer Patients |
| title_full_unstemmed | Integrated Analysis of Single-Cell and Bulk RNA-Sequencing Reveals a Tissue-Resident Macrophage-Related Signature for Predicting Immunotherapy Response in Breast Cancer Patients |
| title_short | Integrated Analysis of Single-Cell and Bulk RNA-Sequencing Reveals a Tissue-Resident Macrophage-Related Signature for Predicting Immunotherapy Response in Breast Cancer Patients |
| title_sort | integrated analysis of single cell and bulk rna sequencing reveals a tissue resident macrophage related signature for predicting immunotherapy response in breast cancer patients |
| topic | breast cancer immune checkpoint therapy tissue-resident macrophages single-cell RNA-sequencing |
| url | https://www.mdpi.com/2072-6694/14/22/5506 |
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