Porcellato Ilaria, Mecocci Samanta, Brachelente Chiara, Cappelli Katia, Armando Federico, Tognoloni Alessia, Chiaradia Elisabetta, Stefanetti Valentina, Mechelli Luca, Pepe Marco, Gialletti Rodolfo, Passeri Benedetta, Ghelardi Alessandro, Razzuoli Elisabetta
Dipartimento di Medicina Veterinaria, Università degli Studi di Perugia, 06126 Perugia, Italy.
Centro di Ricerca sul Cavallo Sportivo, Università degli Studi di Perugia, 06126 Perugia, Italy.
Animals (Basel). 2021 Jul 16;11(7):2121. doi: 10.3390/ani11072121.
In horses, penile squamous cell carcinomas (epSCCs) are among the most common cutaneous neoplastic lesions. These tumors usually arise in benign lesions such as viral plaques and papillomas frequently induced by papillomavirus type 2 (EcPV2) infection. In the last decade, the introduction of immune checkpoint inhibitors (ICI) for the treatment of human cancers has demonstrated promising results. Among the most commonly targeted pathways, there is PD-1/PD-L1 and CTLA-4. The aim of this study is to investigate the expression of the PD-1/PD-L1 pathway and CTLA-4 in the tumor microenvironment of epSCCs to assess the feasibility of an immunotherapeutic approach. Twenty equine epithelial tumors were retrospectively selected and submitted to RT-qPCR for PD-1 and PD-L1 genes. After testing antibodies cross-reactivity by western blotting, immunohistochemistry for PD-L1 and CTLA-4 was performed. Results from RT-qPCR demonstrated that 3/20 cases expressed the gene, whereas the gene was not detected. Immunohistochemical positivity for PD-L1 was found only in one case. CTLA-4-positive cells were observe in all cases but were few (Mdn = 4.8; IQR = 2.3-7.1 cells/HPF). In this study group, PD-1/PD-L1 and CTLA-4 do not appear to be highly expressed and therefore the use of ICI in epSCCs may not have promising rates of response.
在马中，阴茎鳞状细胞癌（epSCCs）是最常见的皮肤肿瘤性病变之一。这些肿瘤通常起源于良性病变，如经常由2型乳头瘤病毒（EcPV2）感染诱发的病毒斑块和乳头瘤。在过去十年中，免疫检查点抑制剂（ICI）用于治疗人类癌症已显示出有前景的结果。在最常靶向的通路中，有PD-1/PD-L1和CTLA-4。本研究的目的是调查PD-1/PD-L1通路和CTLA-4在epSCCs肿瘤微环境中的表达，以评估免疫治疗方法的可行性。回顾性选择了20例马上皮肿瘤，并对其进行PD-1和PD-L1基因的逆转录定量聚合酶链反应（RT-qPCR）。通过蛋白质印迹法检测抗体交叉反应性后，进行了PD-L1和CTLA-4的免疫组织化学检测。RT-qPCR结果显示，20例中有3例表达该基因，而未检测到该基因。仅在1例中发现PD-L1免疫组织化学阳性。在所有病例中均观察到CTLA-4阳性细胞，但数量很少（中位数=4.8；四分位间距=2.3-7.1个细胞/高倍视野）。在该研究组中，PD-1/PD-L1和CTLA-4似乎没有高表达，因此在epSCCs中使用ICI可能没有有前景的反应率。
