Carlos Mario González Zambrano, Fernando Carmona Dinau, Eliana Hurtado Celis, Luis Mauricio Montoya Flórez, João Pessoa Araújo, Luis Fernando Barbisan, Francisco Javier Pedraza Ordoñez, Rogério Antonio de Olivera, Luciane Alarcão Dias-Melicio, Noeme Sousa Rocha
CXCL8 appears to play an important role in the inflammatory microenvironment of CTVT. TP53 intronic polymorphic loci may reflect regulatory variability associated with tumor-host interactions, reinforcing the value of CTVT as a comparative oncology model.
INTRODUCTION: Canine transmissible venereal tumor (CTVT) is a naturally occurring transmissible cancer and an important model in comparative oncology due to its immune evasion mechanisms and tumor-host interactions. Although CTVT usually responds favorably to chemotherapy, variations in tumor behavior suggest the involvement of inflammatory and molecular pathways. CXCL8 is a key mediator of inflammation and immune modulation, whereas the biological significance of TP53 intronic polymorphic loci in CTVT remains poorly understood.
MATERIALS AND METHODS: CTVT samples from dogs in Colombia and Brazil were evaluated for CXCL8 and P53 expression by immunohistochemistry. Polymorphic loci were investigated by Sanger sequencing followed by MUSCLE alignment, genomic remapping, and comparative analysis against canine TP53 reference sequences and previously published canine transmissible tumor genomic datasets. Tumor-associated CD8 + T-cell infiltration was assessed by flow cytometry. Associations among polymorphic loci, inflammatory biomarkers, cytomorphological features, and histopathological parameters were analyzed.
RESULTS AND DISCUSSION: High CXCL8 immunoreactivity was observed in tumor cells and was significantly associated with increased cellular cannibalism. Three TP53 polymorphic loci were identified within an intronic/non-coding region relative to the canine reference sequence KJ511265.1. Two loci showed concordance with previously reported high-confidence (PASS) variants. Tumors harboring polymorphic loci showed increased neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, CD8 + T-cell infiltration, and cytomorphological indicators associated with malignancy.
CONCLUSIONS: CXCL8 appears to play an important role in the inflammatory microenvironment of CTVT. TP53 intronic polymorphic loci may reflect regulatory variability associated with tumor-host interactions, reinforcing the value of CTVT as a comparative oncology model.