Tumor-derived colorectal cancer organoids induce a unique Treg cell population by directing CD4+ T cell differentiation
Summary: In colorectal cancer (CRC), increased numbers of tumor-infiltrating CD4+ regulatory T (Treg) cells correlate with tumor development, immunotherapy failure, and poor prognosis. To assess how CRC tumors directly modulate Treg cell differentiation, we developed an in vitro co-culture system us...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225000872 |
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| author | Sonia Aristin Revilla Cynthia L. Frederiks Stefan Prekovic Enric Mocholi Onno Kranenburg Paul J. Coffer |
| author_facet | Sonia Aristin Revilla Cynthia L. Frederiks Stefan Prekovic Enric Mocholi Onno Kranenburg Paul J. Coffer |
| author_sort | Sonia Aristin Revilla |
| collection | DOAJ |
| description | Summary: In colorectal cancer (CRC), increased numbers of tumor-infiltrating CD4+ regulatory T (Treg) cells correlate with tumor development, immunotherapy failure, and poor prognosis. To assess how CRC tumors directly modulate Treg cell differentiation, we developed an in vitro co-culture system using CD4+ T cells from Foxp3eGFP mice and CRC tumor-derived organoids. Co-culture resulted in a significant increase in Treg cell numbers. RNA-sequencing identified a distinct transcriptional profile of CRC organoid-induced Treg cells, with upregulation of genes associated with CRC Treg cells in vivo. High expression of genes upregulated in CRC organoid-induced Treg cells correlates with shorter progression-free intervals and overall survival in CRC patients. Human CRC organoids similarly induced Treg cells with enhanced suppressive capacity and upregulated genes linked to CRC Treg cells in vivo. This model provides insights into how CRC tumors modulate CD4+ T cell differentiation and can identify approaches to disrupt Treg cells and stimulate anti-tumor immunity. |
| format | Article |
| id | doaj-art-c0771e94ab0547a99a13adf8d8888baf |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-c0771e94ab0547a99a13adf8d8888baf2025-02-07T04:48:03ZengElsevieriScience2589-00422025-02-01282111827Tumor-derived colorectal cancer organoids induce a unique Treg cell population by directing CD4+ T cell differentiationSonia Aristin Revilla0Cynthia L. Frederiks1Stefan Prekovic2Enric Mocholi3Onno Kranenburg4Paul J. Coffer5Center Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands; Laboratory Translational Oncology, University Medical Center Utrecht, Utrecht, the NetherlandsCenter Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands; Laboratory Translational Oncology, University Medical Center Utrecht, Utrecht, the NetherlandsCenter Molecular Medicine, University Medical Center Utrecht, Utrecht, the NetherlandsCenter Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the NetherlandsLaboratory Translational Oncology, University Medical Center Utrecht, Utrecht, the NetherlandsCenter Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands; Corresponding authorSummary: In colorectal cancer (CRC), increased numbers of tumor-infiltrating CD4+ regulatory T (Treg) cells correlate with tumor development, immunotherapy failure, and poor prognosis. To assess how CRC tumors directly modulate Treg cell differentiation, we developed an in vitro co-culture system using CD4+ T cells from Foxp3eGFP mice and CRC tumor-derived organoids. Co-culture resulted in a significant increase in Treg cell numbers. RNA-sequencing identified a distinct transcriptional profile of CRC organoid-induced Treg cells, with upregulation of genes associated with CRC Treg cells in vivo. High expression of genes upregulated in CRC organoid-induced Treg cells correlates with shorter progression-free intervals and overall survival in CRC patients. Human CRC organoids similarly induced Treg cells with enhanced suppressive capacity and upregulated genes linked to CRC Treg cells in vivo. This model provides insights into how CRC tumors modulate CD4+ T cell differentiation and can identify approaches to disrupt Treg cells and stimulate anti-tumor immunity.http://www.sciencedirect.com/science/article/pii/S2589004225000872Immune responseCancerTranscriptomics |
| spellingShingle | Sonia Aristin Revilla Cynthia L. Frederiks Stefan Prekovic Enric Mocholi Onno Kranenburg Paul J. Coffer Tumor-derived colorectal cancer organoids induce a unique Treg cell population by directing CD4+ T cell differentiation iScience Immune response Cancer Transcriptomics |
| title | Tumor-derived colorectal cancer organoids induce a unique Treg cell population by directing CD4+ T cell differentiation |
| title_full | Tumor-derived colorectal cancer organoids induce a unique Treg cell population by directing CD4+ T cell differentiation |
| title_fullStr | Tumor-derived colorectal cancer organoids induce a unique Treg cell population by directing CD4+ T cell differentiation |
| title_full_unstemmed | Tumor-derived colorectal cancer organoids induce a unique Treg cell population by directing CD4+ T cell differentiation |
| title_short | Tumor-derived colorectal cancer organoids induce a unique Treg cell population by directing CD4+ T cell differentiation |
| title_sort | tumor derived colorectal cancer organoids induce a unique treg cell population by directing cd4 t cell differentiation |
| topic | Immune response Cancer Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225000872 |
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