Characterization of canine tumor-infiltrating leukocyte transcriptomic signatures reveals conserved expression patterns with human osteosarcoma
Abstract Immune cells play key roles in host responses to malignant tumors. The selective pressure that immune cells elicit on tumors promotes immune escape, while tumor-associated modulation of immune cells creates an environment favorable to tumor growth and progression. In this study we used publ...
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| Format: | Article |
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Springer
2025-02-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-03950-3 |
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| author | Dylan T. Ammons R. Adam Harris Lyndah Chow Steven Dow |
| author_facet | Dylan T. Ammons R. Adam Harris Lyndah Chow Steven Dow |
| author_sort | Dylan T. Ammons |
| collection | DOAJ |
| description | Abstract Immune cells play key roles in host responses to malignant tumors. The selective pressure that immune cells elicit on tumors promotes immune escape, while tumor-associated modulation of immune cells creates an environment favorable to tumor growth and progression. In this study we used publicly available single-cell RNA sequencing (scRNA-seq) data from the translationally relevant canine osteosarcoma (OS) model to compare tumor-infiltrating immune cells to circulating leukocytes. Through computational analysis we investigated the differences in cell type proportions and how the OS TME impacted infiltrating immune cell transcriptomic profiles relative to circulating leukocytes. Differential abundance analysis revealed increased proportions of follicular helper T cells, regulatory T cells, and mature regulatory dendritic cells (mregDCs) in the OS TME. Differential gene expression analysis identified exhaustion markers (LAG3, HAVCR2, PDCD1) to be upregulated in CD4 and CD8 T cells within the OS TME. Comparisons of B cell gene expression profiles revealed an enrichment of protein processing and endoplasmic reticulum pathways, suggesting infiltrating B cells were activated following tumor infiltration. Gene expression changes within myeloid cells identified increased expression of immune suppressive molecules (CD274, OSM, MSR1) in the OS TME, indicating the TME skews myeloid cells toward an immunosuppressive phenotype. Comparisons to human literature and analysis of human scRNA-seq data revealed conserved transcriptomic responses to tumor infiltration, while also identifying species differences. Overall, the analysis presented here provides new insights into how the OS TME impacts the transcriptional programs of major immune cell populations in dogs and acts as a resource for comparative immuno-oncology research. |
| format | Article |
| id | doaj-art-604b15ea0f554eec94b7a61f092b514d |
| institution | DOAJ |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-604b15ea0f554eec94b7a61f092b514d2025-08-20T03:06:01ZengSpringerCancer Immunology, Immunotherapy1432-08512025-02-0174311810.1007/s00262-025-03950-3Characterization of canine tumor-infiltrating leukocyte transcriptomic signatures reveals conserved expression patterns with human osteosarcomaDylan T. Ammons0R. Adam Harris1Lyndah Chow2Steven Dow3Flint Animal Cancer Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State UniversityDepartment of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State UniversityFlint Animal Cancer Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State UniversityFlint Animal Cancer Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State UniversityAbstract Immune cells play key roles in host responses to malignant tumors. The selective pressure that immune cells elicit on tumors promotes immune escape, while tumor-associated modulation of immune cells creates an environment favorable to tumor growth and progression. In this study we used publicly available single-cell RNA sequencing (scRNA-seq) data from the translationally relevant canine osteosarcoma (OS) model to compare tumor-infiltrating immune cells to circulating leukocytes. Through computational analysis we investigated the differences in cell type proportions and how the OS TME impacted infiltrating immune cell transcriptomic profiles relative to circulating leukocytes. Differential abundance analysis revealed increased proportions of follicular helper T cells, regulatory T cells, and mature regulatory dendritic cells (mregDCs) in the OS TME. Differential gene expression analysis identified exhaustion markers (LAG3, HAVCR2, PDCD1) to be upregulated in CD4 and CD8 T cells within the OS TME. Comparisons of B cell gene expression profiles revealed an enrichment of protein processing and endoplasmic reticulum pathways, suggesting infiltrating B cells were activated following tumor infiltration. Gene expression changes within myeloid cells identified increased expression of immune suppressive molecules (CD274, OSM, MSR1) in the OS TME, indicating the TME skews myeloid cells toward an immunosuppressive phenotype. Comparisons to human literature and analysis of human scRNA-seq data revealed conserved transcriptomic responses to tumor infiltration, while also identifying species differences. Overall, the analysis presented here provides new insights into how the OS TME impacts the transcriptional programs of major immune cell populations in dogs and acts as a resource for comparative immuno-oncology research.https://doi.org/10.1007/s00262-025-03950-3Canine (dog)OsteosarcomascRNA-seqTranscriptomicsCancer immunology |
| spellingShingle | Dylan T. Ammons R. Adam Harris Lyndah Chow Steven Dow Characterization of canine tumor-infiltrating leukocyte transcriptomic signatures reveals conserved expression patterns with human osteosarcoma Cancer Immunology, Immunotherapy Canine (dog) Osteosarcoma scRNA-seq Transcriptomics Cancer immunology |
| title | Characterization of canine tumor-infiltrating leukocyte transcriptomic signatures reveals conserved expression patterns with human osteosarcoma |
| title_full | Characterization of canine tumor-infiltrating leukocyte transcriptomic signatures reveals conserved expression patterns with human osteosarcoma |
| title_fullStr | Characterization of canine tumor-infiltrating leukocyte transcriptomic signatures reveals conserved expression patterns with human osteosarcoma |
| title_full_unstemmed | Characterization of canine tumor-infiltrating leukocyte transcriptomic signatures reveals conserved expression patterns with human osteosarcoma |
| title_short | Characterization of canine tumor-infiltrating leukocyte transcriptomic signatures reveals conserved expression patterns with human osteosarcoma |
| title_sort | characterization of canine tumor infiltrating leukocyte transcriptomic signatures reveals conserved expression patterns with human osteosarcoma |
| topic | Canine (dog) Osteosarcoma scRNA-seq Transcriptomics Cancer immunology |
| url | https://doi.org/10.1007/s00262-025-03950-3 |
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