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犬类免疫检查点抑制剂:我们准备好了吗?

英文原题:Checkpoint Inhibitors in Dogs: Are We There Yet?

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Checkpoint Inhibitors in Dogs: Are We There Yet?

PubMed 2024/05/24(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

免疫检查点抑制剂(ICI)已经彻底改变了人类的癌症治疗。免疫检查点是机体对免疫刺激反应的重要调节因子。研究最多的免疫检查点分子是程序性死亡(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)及其配体CD80(B7-1)和CD86(B7-2)。某些肿瘤可以通过激活这些免疫检查点靶点来逃避免疫监视。这些蛋白在癌细胞和TIL(肿瘤浸润淋巴细胞)中常常上调,使癌细胞能够逃避免疫监视并促进肿瘤生长。通过阻断抑制性检查点,ICI可以帮助恢复免疫系统有效对抗癌症。多项研究已经探讨了这些及其他免疫检查点在人类癌症中的表达,并显示了它们作为治疗靶点的潜力。近年来,研究犬类癌症中免疫检查点表达的兴趣日益增长,并且已经在这些物种中开展了一些小型ICI临床试验。兽医肿瘤学中的新兴研究集中在开发和验证犬类靶向抗体。在ICI中,抗PD-1和抗PD-L1治疗最为突出,是最有前景的,这与过去十年人类医学中的成功相呼应。

然而,犬源化抗体的疗效仍然不够理想,尤其是对于犬口腔黑色素瘤。为了提高ICI的利用率,识别治疗反应的预测性生物标志物以及对个体肿瘤进行全面筛查至关重要。这些努力有望推动兽医实践中的个性化医疗,从而改善治疗结果。本文旨在综述目前关于犬类癌症中免疫检查点表达的研究文献以及ICI在犬类中治疗的当前结果。

展开英文摘要原文

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.

论文信息

作者
Giuliano A、Pimentel PAB、Horta RS
第一作者单位
Department of Veterinary Clinical Science, Jockey Club College of Veterinary Medicine, City University of Hong Kong, Hong Kong, China.Hong Kong
通讯作者单位
Department of Veterinary Medicine and Surgery, Veterinary School, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, MG, Brazil.Brazil
文献类型
综述
期刊
Cancers2024 May 24
原文标识
PubMed 38893123 · DOI 10.3390/cancers16112003