Immune checkpoint inhibitors (ICI) have revolutionised cancer treatment in people. Immune checkpoints are important regulators of the body’s reaction to immunological stimuli. The most studied immune checkpoint molecules are programmed death (PD-1) with its ligand (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) with its ligands CD80 (B7-1) and CD86 (B7-2). Certain tumours can evade immunosurveillance by activating these immunological checkpoint targets. These proteins are often upregulated in cancer cells and tumour-infiltrating lymphocytes, allowing cancer cells to evade immune surveillance and promote tumour growth. By blocking inhibitory checkpoints, ICI can help restore the immune system to effectively fight cancer. Several studies have investigated the expression of these and other immune checkpoints in human cancers and have shown their potential as therapeutic targets. In recent years, there has been growing interest in studying the expression of immune checkpoints in dogs with cancer, and a few small clinical trials with ICI have already been performed on these species. Emerging studies in veterinary oncology are centred around developing and validating canine-targeted antibodies. Among ICIs, anti-PD-1 and anti-PD-L1 treatments stand out as the most promising, mirroring the success in human medicine over the past decade. Nevertheless, the efficacy of caninized antibodies remains suboptimal, especially for canine oral melanoma. To enhance the utilisation of ICIs, the identification of predictive biomarkers for treatment response and the thorough screening of individual tumours are crucial. Such endeavours hold promise for advancing personalised medicine within veterinary practice, thereby improving treatment outcomes. This article aims to review the current research literature about the expression of immune checkpoints in canine cancer and the current results of ICI treatment in dogs.
免疫检查点抑制剂（ICI）已彻底改变人类癌症治疗模式。免疫检查点是机体对免疫刺激反应的重要调节因子，其中研究最为深入的是程序性死亡受体-1（PD-1）及其配体（PD-L1），以及细胞毒性T淋巴细胞相关蛋白4（CTLA-4）与其配体CD80（B7-1）和CD86（B7-2）。特定肿瘤可通过激活这些免疫检查点靶标逃避免疫监视。这些蛋白在癌细胞和肿瘤浸润淋巴细胞中常呈现高表达，使癌细胞能够规避免疫监视并促进肿瘤生长。通过阻断抑制性检查点，ICI可帮助恢复免疫系统有效抗击癌症的能力。 多项研究已证实这些免疫检查点分子在人类癌症中的表达特征，并揭示其作为治疗靶点的潜力。近年来，犬类癌症免疫检查点表达研究日益受到关注，已有若干针对犬类的小规模ICI临床试验。兽医肿瘤学新兴研究聚焦于犬源化抗体的开发与验证，其中抗PD-1/PD-L1疗法展现出与人类医学近十年成功经验相呼应的应用前景。然而犬源化抗体疗效尚未达到理想状态，尤其在犬口腔黑色素瘤治疗中表现尤为明显。 为提升ICI疗效，识别治疗反应的预测性生物标志物及开展个体化肿瘤全面筛查至关重要。这些研究将推动兽医临床个性化医疗发展，从而改善治疗结局。本文旨在综述当前关于犬类癌症免疫检查点表达特征及ICI治疗成效的研究文献。
肿瘤(癌症)患者之家