Lady Davis Institute, Jewish General Hospital, Translational Center for Research in Cancer, McGill University, Montreal, QC, Canada.
Oncology and Experimental Medicine, McGill University, Montreal, QC, Canada.
Front Immunol. 2020 Sep 29;11:564499. doi: 10.3389/fimmu.2020.564499. eCollection 2020.
Though a healthy immune system is capable of recognizing and eliminating emergent cancerous cells, an established tumor is adept at escaping immune surveillance. Altered and tumor-specific expression of immunosuppressive cell surface carbohydrates, also termed the "tumor glycocode," is a prominent mechanism by which tumors can escape anti-tumor immunity. Given their persistent and homogeneous expression, tumor-associated glycans are promising targets to be exploited as biomarkers and therapeutic targets. However, the exploitation of these glycans has been a challenge due to their low immunogenicity, immunosuppressive properties, and the inefficient presentation of glycolipids in a conventional major histocompatibility complex (MHC)-restricted manner. Despite this, a subset of T-cells expressing the gamma and delta chains of the T-cell receptor (γδ T cells) exist with a capacity for MHC-unrestricted antigen recognition and potent inherent anti-tumor properties. In this review, we discuss the role of tumor-associated glycans in anti-tumor immunity, with an emphasis on the potential of γδ T cells to target the tumor glycocode. Understanding the many facets of this interaction holds the potential to unlock new ways to use both tumor-associated glycans and γδ T cells in novel therapeutic interventions.
虽然健康的免疫系统能够识别和消除新出现的癌细胞，但已建立的肿瘤善于逃避免疫监视。免疫抑制性细胞表面碳水化合物的改变和肿瘤特异性表达，也称为“肿瘤糖码”，是肿瘤逃避抗肿瘤免疫的主要机制之一。鉴于其持续和同质的表达，肿瘤相关聚糖是有希望被用作生物标志物和治疗靶点的候选物。然而，由于其免疫原性低、免疫抑制特性以及糖脂在传统的主要组织相容性复合体（MHC）受限方式下的低效呈递，这些聚糖的利用一直是一个挑战。尽管如此，仍存在一部分表达 T 细胞受体（TCR）γ和δ链的 T 细胞（γδ T 细胞），具有 MHC 非限制性抗原识别能力和潜在的强大抗肿瘤特性。在这篇综述中，我们讨论了肿瘤相关聚糖在抗肿瘤免疫中的作用，重点介绍了 γδ T 细胞靶向肿瘤糖码的潜力。了解这种相互作用的多个方面有可能为利用肿瘤相关聚糖和 γδ T 细胞开辟新的治疗干预途径提供新的思路。
