Nascimento Catarina, Urbano Ana Catarina, Gameiro Andreia, Ferreira João, Correia Jorge, Ferreira Fernando
CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Cancers (Basel). 2020 May 28;12(6):1386. doi: 10.3390/cancers12061386.
Tumor microenvironment has gained great relevance due to its ability to regulate distinct checkpoints mediators, orchestrating tumor progression. Serum programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) levels were compared with healthy controls and with serum cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and tumor necrosis factor-alpha (TNF-α) levels in order to understand the role of PD-1/PD-L1 axis in cats with mammary carcinoma. PD-1 and PD-L1 expression was evaluated in tumor-infiltrating lymphocytes (TILs) and cancer cells, as the presence of somatic mutations. Results showed that serum PD-1 and PD-L1 levels were significantly higher in cats with HER2-positive ( = 0.017; = 0.032) and triple negative (TN) normal-like mammary carcinomas ( = 0.004; = 0.015), showing a strong positive correlation between serum CTLA-4 and TNF-α levels. In tumors, PD-L1 expression in cancer cells was significantly higher in HER2-positive samples than in TN normal-like tumors ( = 0.010), as the percentage of PD-L1-positive TILs ( = 0.037). gene sequencing identified two heterozygous mutations in exon 4 (A245T; V252M) and one in exon 5 (T267S). In summary, results support the use of spontaneous feline mammary carcinoma as a model for human breast cancer and suggest that the development of monoclonal antibodies may be a therapeutic strategy.
肿瘤微环境因其调节不同检查点介质、协调肿瘤进展的能力而变得至关重要。将血清程序性细胞死亡蛋白1（PD-1）和程序性死亡配体1（PD-L1）水平与健康对照进行比较，并与血清细胞毒性T淋巴细胞相关抗原4（CTLA-4）和肿瘤坏死因子-α（TNF-α）水平进行比较，以了解PD-1/PD-L1轴在猫乳腺癌中的作用。评估肿瘤浸润淋巴细胞（TILs）和癌细胞中PD-1和PD-L1的表达，以及体细胞突变的存在情况。结果显示，HER2阳性（P = 0.017；P = 0.032）和三阴性（TN）正常样乳腺癌猫的血清PD-1和PD-L1水平显著更高（P = 0.004；P = 0.015），血清CTLA-4和TNF-α水平之间呈强正相关。在肿瘤中，HER2阳性样本中癌细胞的PD-L1表达显著高于TN正常样肿瘤（P = 0.010），PD-L1阳性TILs的百分比也是如此（P = 0.037）。基因测序在第4外显子中鉴定出两个杂合突变（A245T；V252M），在第5外显子中鉴定出一个突变（T267S）。总之，结果支持将自发性猫乳腺癌用作人类乳腺癌的模型，并表明单克隆抗体的开发可能是一种治疗策略。
