Ribeiro Mariana Pinto, Canadas-Sousa Ana, Aluai-Cunha Catarina, de Fátima Carvalho Maria, Santos Andreia Ferreira
Department of Veterinary Clinics, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
Vet Comp Oncol. 2025 Mar;23(1):109-115. doi: 10.1111/vco.13036. Epub 2024 Dec 19.
Mast cell tumours (MCTs) are the most frequent cutaneous neoplasia of the dog, and they have very variable biological behaviour and survival times. Surgery is still the best treatment, and despite the several adjuvant therapies described, many cases are very aggressive and resistant to these treatments making it urgent to find new therapeutic targets. Nowadays, immunotherapy targeting immune checkpoints has been described as a complementary treatment for several human cancers, but it is still very scarcely studied in veterinary medicine. Therefore, this study aimed to investigate the expression of the checkpoint proteins programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) to evaluate their potential as therapeutic targets for MCT. Through immunohistochemical study, it was analysed the expression of PD-L1 and CTLA-4 in 74 MCT cases from the archive of the Veterinary Pathology Laboratory of the University of Porto (LabPatVet). Tumour size, histological grade, ki-67 proliferation index, mitotic count and presence of metastatic disease were also assessed. Most of the cases expressed both immune checkpoints in neoplastic cells. There was a statistically significant inverse association between the expression of CTLA-4 and MCT grade (p < 0,001) and mitotic count (p < 0.001). PD-L1 was significantly and negatively related to HG (p = 0.004), and tumour size (р = 0.014). Tumour size, histological grade and mitotic count were positively associated with metastatic disease. Additionally, it was observed that the expression of PD-L1 and CTLA-4 was interrelated (p < 0.001). This study demonstrated that MCT cells express both PD-L1 and CTLA-4 and that their expression was associated with MCT prognostic factors.
肥大细胞瘤（MCTs）是犬类最常见的皮肤肿瘤，其生物学行为和生存时间差异很大。手术仍然是最佳治疗方法，尽管有多种辅助治疗方法，但许多病例具有很强的侵袭性且对这些治疗有抗性，因此迫切需要寻找新的治疗靶点。如今，针对免疫检查点的免疫疗法已被描述为几种人类癌症的辅助治疗方法，但在兽医学中仍研究甚少。因此，本研究旨在调查检查点蛋白程序性死亡配体1（PD-L1）和细胞毒性T淋巴细胞抗原4（CTLA-4）的表达，以评估它们作为MCT治疗靶点的潜力。通过免疫组织化学研究，分析了来自波尔图大学兽医病理学实验室（LabPatVet）存档的74例MCT病例中PD-L1和CTLA-4的表达。还评估了肿瘤大小、组织学分级、ki-67增殖指数、有丝分裂计数和转移疾病的存在情况。大多数病例在肿瘤细胞中同时表达两种免疫检查点。CTLA-4的表达与MCT分级（p < 0.001）和有丝分裂计数（p < 0.001）之间存在统计学上显著的负相关。PD-L1与高级别（HG）（p = 0.004）和肿瘤大小（р = 0.014）显著负相关。肿瘤大小、组织学分级和有丝分裂计数与转移疾病呈正相关。此外，观察到PD-L1和CTLA-4的表达相互关联（p < 0.001）。本研究表明，MCT细胞同时表达PD-L1和CTLA-4，且它们的表达与MCT预后因素相关。
