Transcriptomics of Canine Inflammatory Mammary Cancer Treated with Empty Cowpea Mosaic Virus Implicates Neutrophils in Anti-Tumor Immunity.
Lucia BarrenoNatalia SevaneGuillermo ValdiviaDaniel Alonso-MiguelMaria Suarez-RedondoAngela Alonso-DiezSteven FieringVeronique BeissNicole F SteinmetzMaria Dolores Perez-AlenzaLaura PeñaPublished in: International journal of molecular sciences (2023)
Canine inflammatory mammary cancer (IMC) is a highly aggressive and lethal cancer in dogs serving as a valuable animal model for its human counterpart, inflammatory breast cancer (IBC), both lacking effective therapies. Intratumoral immunotherapy (IT-IT) with empty cowpea mosaic virus (eCPMV) nanoparticles has shown promising results, demonstrating a reduction in tumor size, longer survival rates, and improved quality of life. This study compares the transcriptomic profiles of tumor samples from female dogs with IMC receiving eCPMV IT-IT and medical therapy (MT) versus MT alone. Transcriptomic analyses, gene expression profiles, signaling pathways, and cell type profiling of immune cell populations in samples from four eCPMV-treated dogs with IMC and four dogs with IMC treated with MT were evaluated using NanoString Technologies using a canine immune-oncology panel. Comparative analyses revealed 34 differentially expressed genes between treated and untreated samples. Five genes ( CXCL8 , S100A9 , CCL20 , IL6 , and PTGS2 ) involved in neutrophil recruitment and activation were upregulated in the treated samples, linked to the IL17-signaling pathway. Cell type profiling showed a significant increase in neutrophil populations in the tumor microenvironment after eCPMV treatment. These findings highlight the role of neutrophils in the anti-tumor response mediated by eCPMV IT-IT and suggest eCPMV as a novel therapeutic approach for IBC/IMC.
Keyphrases
- single cell
- papillary thyroid
- signaling pathway
- squamous cell
- oxidative stress
- genome wide
- healthcare
- endothelial cells
- rna seq
- newly diagnosed
- squamous cell carcinoma
- stem cells
- palliative care
- genome wide identification
- bone marrow
- epithelial mesenchymal transition
- cell proliferation
- dna methylation
- transcription factor
- bioinformatics analysis