Dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single-cell and bulk transcriptome analysis
Abstract Background Cellular states of different immune cells can affect the activity of the whole immune microenvironment. Methods Here, leveraging reference profiles of microenvironment cell states that were constructed based on single-cell RNA-seq data of melanoma, we dissected the composition of...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | BMC Immunology |
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| Online Access: | https://doi.org/10.1186/s12865-023-00587-8 |
| _version_ | 1797388402943852544 |
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| author | Aiai Shi Min Yan Bo Pang Lin Pang Yihan Wang Yujia Lan Xinxin Zhang Jinyuan Xu Yanyan Ping Jing Hu |
| author_facet | Aiai Shi Min Yan Bo Pang Lin Pang Yihan Wang Yujia Lan Xinxin Zhang Jinyuan Xu Yanyan Ping Jing Hu |
| author_sort | Aiai Shi |
| collection | DOAJ |
| description | Abstract Background Cellular states of different immune cells can affect the activity of the whole immune microenvironment. Methods Here, leveraging reference profiles of microenvironment cell states that were constructed based on single-cell RNA-seq data of melanoma, we dissected the composition of microenvironment cell states across 463 skin cutaneous melanoma (SKCM) bulk samples through CIBERSORT-based deconvolution of gene expression profiles and revealed high heterogeneity of their distribution. Correspondence analysis on the estimated cellular fractions of melanoma bulk samples was performed to identify immune phenotypes. Based on the publicly available clinical survival and therapy data, we analyzed the relationship between immune phenotypes and clinical outcomes of melanoma. Results By analysis of the relationships among those cell states, we further identified three distinct tumor microenvironment immune phenotypes: “immune hot/active”, “immune cold-suppressive” and “immune cold-exhausted”. They were characterized by markedly different patterns of cell states: most notably the CD8 T Cytotoxic state, CD8 T Mixed state, B non-regulatory state and cancer-associated fibroblasts (CAFs), depicting distinct types of antitumor immune response (or immune activity). These phenotypes had prognostic significance for progression-free survival and implications in response to immune therapy in an independent cohort of anti-PD1 treated melanoma patients. Conclusions The proposed strategy of leveraging single-cell data to dissect the composition of microenvironment cell states in individual bulk tumors can also extend to other cancer types, and our results highlight the importance of microenvironment cell states for the understanding of tumor immunity. |
| first_indexed | 2024-03-08T22:40:19Z |
| format | Article |
| id | doaj.art-521fbd8bd2f64c038a67a4edc2d6785a |
| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-03-08T22:40:19Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj.art-521fbd8bd2f64c038a67a4edc2d6785a2023-12-17T12:11:48ZengBMCBMC Immunology1471-21722023-12-0124111710.1186/s12865-023-00587-8Dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single-cell and bulk transcriptome analysisAiai Shi0Min Yan1Bo Pang2Lin Pang3Yihan Wang4Yujia Lan5Xinxin Zhang6Jinyuan Xu7Yanyan Ping8Jing Hu9School of Intelligent Medicine and Biotechnology, Guilin Medical UniversityDepartment of Immunology, College of Basic Medicine, Chongqing Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityAbstract Background Cellular states of different immune cells can affect the activity of the whole immune microenvironment. Methods Here, leveraging reference profiles of microenvironment cell states that were constructed based on single-cell RNA-seq data of melanoma, we dissected the composition of microenvironment cell states across 463 skin cutaneous melanoma (SKCM) bulk samples through CIBERSORT-based deconvolution of gene expression profiles and revealed high heterogeneity of their distribution. Correspondence analysis on the estimated cellular fractions of melanoma bulk samples was performed to identify immune phenotypes. Based on the publicly available clinical survival and therapy data, we analyzed the relationship between immune phenotypes and clinical outcomes of melanoma. Results By analysis of the relationships among those cell states, we further identified three distinct tumor microenvironment immune phenotypes: “immune hot/active”, “immune cold-suppressive” and “immune cold-exhausted”. They were characterized by markedly different patterns of cell states: most notably the CD8 T Cytotoxic state, CD8 T Mixed state, B non-regulatory state and cancer-associated fibroblasts (CAFs), depicting distinct types of antitumor immune response (or immune activity). These phenotypes had prognostic significance for progression-free survival and implications in response to immune therapy in an independent cohort of anti-PD1 treated melanoma patients. Conclusions The proposed strategy of leveraging single-cell data to dissect the composition of microenvironment cell states in individual bulk tumors can also extend to other cancer types, and our results highlight the importance of microenvironment cell states for the understanding of tumor immunity.https://doi.org/10.1186/s12865-023-00587-8Cell statesMicroenvironmentImmune phenotypeImmunotherapyMelanoma |
| spellingShingle | Aiai Shi Min Yan Bo Pang Lin Pang Yihan Wang Yujia Lan Xinxin Zhang Jinyuan Xu Yanyan Ping Jing Hu Dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single-cell and bulk transcriptome analysis BMC Immunology Cell states Microenvironment Immune phenotype Immunotherapy Melanoma |
| title | Dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single-cell and bulk transcriptome analysis |
| title_full | Dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single-cell and bulk transcriptome analysis |
| title_fullStr | Dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single-cell and bulk transcriptome analysis |
| title_full_unstemmed | Dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single-cell and bulk transcriptome analysis |
| title_short | Dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single-cell and bulk transcriptome analysis |
| title_sort | dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single cell and bulk transcriptome analysis |
| topic | Cell states Microenvironment Immune phenotype Immunotherapy Melanoma |
| url | https://doi.org/10.1186/s12865-023-00587-8 |
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