Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam, the Netherlands.
Cancer Center Amsterdam, Amsterdam, the Netherlands.
Br J Dermatol. 2024 Apr 17;190(5):627-635. doi: 10.1093/bjd/ljad517.
Modulation of immune responses through immune checkpoint blockade has revolutionized cutaneous melanoma treatment. However, it is still the case that not all patients respond successfully to these therapies, indicating the presence of as yet unknown resistance mechanisms. Hence, it is crucial to find novel targets to improve therapy efficacy. One of the described resistance mechanisms is regulated by immune inhibitory Siglec receptors, which are engaged by the carbohydrates sialic acids expressed on tumour cells, contributing to programmed cell death protein-1 (PD1)-like immune suppression mechanisms. In this review, we provide an overview on the regulation of sialic acid synthesis, its expression in melanoma, and the contribution of the sialic acid-Siglec axis to tumour development and immune suppressive mechanisms in the tumour microenvironment. Finally, we highlight potential sialic acid-Siglec axis-related therapeutics to improve the treatment of melanoma.
通过免疫检查点阻断来调节免疫反应已经彻底改变了皮肤黑色素瘤的治疗方法。然而，并非所有患者对这些治疗都能成功响应，这表明存在尚未被发现的耐药机制。因此，找到新的靶点来提高治疗效果至关重要。其中一种描述的耐药机制受免疫抑制性 Siglec 受体调节，这些受体与肿瘤细胞上表达的碳水化合物唾液酸结合，有助于程序性死亡蛋白-1（PD1）样免疫抑制机制。在这篇综述中，我们概述了唾液酸合成的调控、黑色素瘤中的表达以及唾液酸-Siglec 轴在肿瘤发展和肿瘤微环境中的免疫抑制机制中的作用。最后，我们强调了潜在的与唾液酸-Siglec 轴相关的治疗方法，以改善黑色素瘤的治疗效果。
