Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer
Abstract Background Overweight and obesity are established risk factors for various types of cancers including colorectal cancer (CRC). However the underlying molecular mechanisms remain unclear. An in-depth understanding of the oncologic characteristics of overweight and obese CRC at the single-cel...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-04921-5 |
| _version_ | 1797273448862449664 |
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| author | Guozhong Xiao Yihui Zheng Huaxian Chen Minyi Luo Chaoxin Yang Donglin Ren Pengfei Qin Heng Zhang Hongcheng Lin |
| author_facet | Guozhong Xiao Yihui Zheng Huaxian Chen Minyi Luo Chaoxin Yang Donglin Ren Pengfei Qin Heng Zhang Hongcheng Lin |
| author_sort | Guozhong Xiao |
| collection | DOAJ |
| description | Abstract Background Overweight and obesity are established risk factors for various types of cancers including colorectal cancer (CRC). However the underlying molecular mechanisms remain unclear. An in-depth understanding of the oncologic characteristics of overweight and obese CRC at the single-cell level can provide valuable insights for the development of more effective treatment strategies for CRC. Methods We conducted single-cell RNA sequencing (scRNA-seq) analysis on tumor and adjacent normal colorectal samples from 15 overweight/obese and 15 normal-weight CRC patients. Immunological and metabolic differences between overweight/obese CRC and non-obese CRC were characterized. Results We obtained single-cell transcriptomics data from a total of 192,785 cells across all samples. By evaluating marker gene expression patterns, we annotated nine main cell types in the CRC ecosystem. Specifically, we found that the cytotoxic function of effector T cells and NK cells was impaired in overweight/obese CRC compared with non-obese CRC, relating to its metabolic dysregulation. CD4+T cells in overweight/obese CRC exhibited higher expression of immune checkpoint molecules. The antigen-presenting ability of DCs and B cells is down-regulated in overweight/obese CRC, which may further aggravate the immunosuppression of overweight/obese CRC. Additionally, dysfunctional stromal cells were identified, potentially promoting invasion and metastasis in overweight/obese CRC. Furthermore, we discovered the up-regulated metabolism of glycolysis and lipids of tumor cells in overweight/obese CRC, which may impact the metabolism and function of immune cells. We also identified inhibitory interactions between tumor cells and T cells in overweight/obese CRC. Conclusions The study demonstrated that overweight/obese CRC has a more immunosuppressive microenvironment and distinct metabolic reprogramming characterized by increased of glycolysis and lipid metabolism. These findings may have implications for the development of novel therapeutic strategies for overweight/obese CRC patients. |
| first_indexed | 2024-03-07T14:43:25Z |
| format | Article |
| id | doaj.art-2972979d45144daea593c7a0941d8072 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-07T14:43:25Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-2972979d45144daea593c7a0941d80722024-03-05T20:07:13ZengBMCJournal of Translational Medicine1479-58762024-02-0122112110.1186/s12967-024-04921-5Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancerGuozhong Xiao0Yihui Zheng1Huaxian Chen2Minyi Luo3Chaoxin Yang4Donglin Ren5Pengfei Qin6Heng Zhang7Hongcheng Lin8Department of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-Sen UniversityBGI ResearchDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-Sen UniversityAbstract Background Overweight and obesity are established risk factors for various types of cancers including colorectal cancer (CRC). However the underlying molecular mechanisms remain unclear. An in-depth understanding of the oncologic characteristics of overweight and obese CRC at the single-cell level can provide valuable insights for the development of more effective treatment strategies for CRC. Methods We conducted single-cell RNA sequencing (scRNA-seq) analysis on tumor and adjacent normal colorectal samples from 15 overweight/obese and 15 normal-weight CRC patients. Immunological and metabolic differences between overweight/obese CRC and non-obese CRC were characterized. Results We obtained single-cell transcriptomics data from a total of 192,785 cells across all samples. By evaluating marker gene expression patterns, we annotated nine main cell types in the CRC ecosystem. Specifically, we found that the cytotoxic function of effector T cells and NK cells was impaired in overweight/obese CRC compared with non-obese CRC, relating to its metabolic dysregulation. CD4+T cells in overweight/obese CRC exhibited higher expression of immune checkpoint molecules. The antigen-presenting ability of DCs and B cells is down-regulated in overweight/obese CRC, which may further aggravate the immunosuppression of overweight/obese CRC. Additionally, dysfunctional stromal cells were identified, potentially promoting invasion and metastasis in overweight/obese CRC. Furthermore, we discovered the up-regulated metabolism of glycolysis and lipids of tumor cells in overweight/obese CRC, which may impact the metabolism and function of immune cells. We also identified inhibitory interactions between tumor cells and T cells in overweight/obese CRC. Conclusions The study demonstrated that overweight/obese CRC has a more immunosuppressive microenvironment and distinct metabolic reprogramming characterized by increased of glycolysis and lipid metabolism. These findings may have implications for the development of novel therapeutic strategies for overweight/obese CRC patients.https://doi.org/10.1186/s12967-024-04921-5Colorectal cancerOverweightObesityObeseSingle-cell RNA sequencingTumor microenvironment |
| spellingShingle | Guozhong Xiao Yihui Zheng Huaxian Chen Minyi Luo Chaoxin Yang Donglin Ren Pengfei Qin Heng Zhang Hongcheng Lin Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer Journal of Translational Medicine Colorectal cancer Overweight Obesity Obese Single-cell RNA sequencing Tumor microenvironment |
| title | Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer |
| title_full | Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer |
| title_fullStr | Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer |
| title_full_unstemmed | Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer |
| title_short | Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer |
| title_sort | single cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer |
| topic | Colorectal cancer Overweight Obesity Obese Single-cell RNA sequencing Tumor microenvironment |
| url | https://doi.org/10.1186/s12967-024-04921-5 |
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