Bovine ocular squamous cell carcinoma (BOSCC) constitutes a malignant epithelial neoplasm that has been linked to causative influences including ultraviolet light exposure and lack of pigment. Serving as key elements of the innate immune system, Toll-like receptors (TLRs) orchestrate inflammatory and immune reactions by sensing both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Through the NF-κB pathway, TLR signal transduction exerts dualistic actions in tumor development thereby promoting inflammation while simultaneously inhibiting programmed cell death. The Bcl-2 protein family governs apoptotic processes, whereas matrix metalloproteinases (MMPs) hold crucial importance for tissue invasion and metastatic spread. In this study, TLR3 and TLR9 expressions in BOSCC were evaluated by immunohisto-chemistry and immunofluorescence and the relationships between Bax, Bcl-2, and MMP-9 were also investigated. TLR3 and TLR9 were highly expressed irrespective of tumor differentiation and did not show a strong direct correlation with apoptotic and invasion markers. However, in poorly differentiated cases, a significant increase in Bcl-2 and a relative decrease in Bax indicated a shift towards an anti-apoptotic phenotype. The high expression of TLR3/9 suggested that it may have the potential to be an immunotherapeutic target rather than an independent biomarker. The Bcl-2/Bax ratio increased from 0.26 in well-differentiated cases to 0.67 in poorly differentiated cases. An increased Bcl-2/Bax ratio suggests apoptosis resistance and this situation may explain resistance to conventional treatments and suggests that a combination of Bcl-2 inhibitors and immunotherapy may be beneficial.

To Cite This Article: Nuhoğlu H, Kengiş M, Uysal YA and Dağ S, 2026. Investigation of the Relationship Between TLR-3/9 Expressions and Apoptotic Markers in Bovine BOSCC Cases Using Immunohistochemical Methods. Pak Vet J, 46(6): 1429-1438. http://dx.doi.org/10.29261/pakvetj/2026.137