Hegde Mangala, Girisa Sosmitha, Aswani Babu Santha, Alqahtani Mohammed S, Abbas Mohamed, Sethi Gautam, Kunnumakkara Ajaikumar B
Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India.
Radiological Sciences Department, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia; BioImaging Unit, Space Research Centre, Michael Atiyah Building, University of Leicester, Leicester LE1 7RH, UK.
Life Sci. 2024 Aug 15;351:122786. doi: 10.1016/j.lfs.2024.122786. Epub 2024 Jun 5.
Gangliosides represent glycolipids containing sialic acid residues, present on the cell membrane with glycan residues exposed to the extracellular matrix (ECM), while the ceramides are anchored within the membrane. These molecules play a critical role in pathophysiological processes such as host-pathogen interactions, cell-cell recognition, signal transduction, cell adhesion, motility, and immunomodulation. Accumulated evidence suggests the overexpression of gangliosides on tumor tissues in comparison to healthy human tissues. These tumor-associated gangliosides have been implicated in various facets of tumor biology, including cell motility, differentiation, signaling, immunosuppression, angiogenesis, and metastasis. Consequently, these entities emerge as attractive targets for immunotherapeutic interventions. Notably, the administration of antibodies targeting gangliosides has demonstrated cytotoxic effects on cancer cells that exhibit an overexpression of these glycolipids. Passive immunotherapy approaches utilizing murine or murine/human chimeric anti-ganglioside antibodies have been explored as potential treatments for diverse cancer types. Additionally, vaccination strategies employing tumor-associated gangliosides in conjunction with adjuvants have entered the realm of promising techniques currently undergoing clinical trials. The present comprehensive review encapsulates the multifaceted roles of gangliosides in tumor initiation, progression, immunosuppression, and metastasis. Further, an overview is provided of the correlation between the expression status of gangliosides in normal and tumor cells and its impact on cancer patient survival. Furthermore, the discussion extends to ongoing and completed clinical trials employing diverse strategies to target gangliosides, elucidating their effectiveness in treating cancers. This emerging discipline is expected to supply substantial impetus for the establishment of novel therapeutic strategies.
神经节苷脂是含有唾液酸残基的糖脂，存在于细胞膜上，其聚糖残基暴露于细胞外基质（ECM）中，而神经酰胺则锚定在膜内。这些分子在宿主-病原体相互作用、细胞-细胞识别、信号转导、细胞黏附、运动和免疫调节等病理生理过程中发挥着关键作用。越来越多的证据表明，与健康人体组织相比，肿瘤组织中神经节苷脂过度表达。这些肿瘤相关神经节苷脂与肿瘤生物学的各个方面有关，包括细胞运动、分化、信号传导、免疫抑制、血管生成和转移。因此，这些物质成为免疫治疗干预的有吸引力的靶点。值得注意的是，靶向神经节苷脂的抗体给药已证明对过度表达这些糖脂的癌细胞具有细胞毒性作用。利用鼠源或鼠/人嵌合抗神经节苷脂抗体的被动免疫治疗方法已被探索作为多种癌症类型的潜在治疗方法。此外，将肿瘤相关神经节苷脂与佐剂联合使用的疫苗接种策略已进入目前正在进行临床试验的有前景的技术领域。本综述全面总结了神经节苷脂在肿瘤发生、进展、免疫抑制和转移中的多方面作用。此外，还概述了神经节苷脂在正常细胞和肿瘤细胞中的表达状态与其对癌症患者生存影响之间的相关性。此外，讨论还扩展到采用多种策略靶向神经节苷脂的正在进行和已完成的临床试验，阐明它们在治疗癌症方面的有效性。这一新兴学科有望为建立新的治疗策略提供巨大动力。
