Department of Chemistry, School of Science and Engineering, The American University in Cairo, New Cairo, Cairo, 11835, Egypt.
Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt.
Lipids Health Dis. 2021 Oct 31;20(1):150. doi: 10.1186/s12944-021-01581-y.
Cell surface biochemical changes, notably excessive increase in outer leaflet sphingomyelin (SM) content, are important in cancer initiation, growth, and immune evasion. Innumerable reports describe methods to initiate, promote, or enhance immunotherapy of clinically detected cancer, notwithstanding the challenges, if not impossibility, of identification of tumor-specific, or associated antigens, the lack of tumor cell surface membrane expression of major histocompatibility complex (MHC) class I alpha and β2 microglobulin chains, and lack of expression or accessibility of Fas and other natural killer cell immune checkpoint molecules. Conversely, SM synthesis and hydrolysis are increasingly implicated in initiation of carcinogenesis and promotion of metastasis. Surface membrane SM readily forms inter- and intra- molecular hydrogen bond network, which excessive tightness would impair cell-cell contact inhibition, inter- and intra-cellular signals, metabolic pathways, and susceptibility to host immune cells and mediators. The present review aims at clarifying the tumor immune escape mechanisms, which face common immunotherapeutic approaches, and attracting attention to an entirely different, neglected, key aspect of tumorigenesis associated with biochemical changes in the cell surface that lead to failure of contact inhibition, an instrumental tumorigenesis mechanism. Additionally, the review aims to provide evidence for surface membrane SM levels and roles in cells resistance to death, failure to respond to growth suppressor signals, and immune escape, and to suggest possible novel approaches to cancer control and cure.
细胞表面生化变化，特别是外小叶鞘磷脂（SM）含量的过度增加，在癌症的发生、生长和免疫逃逸中非常重要。无数报告描述了启动、促进或增强临床检测到的癌症的免疫疗法的方法，尽管存在挑战，如果不是不可能的话，确定肿瘤特异性或相关抗原、主要组织相容性复合体（MHC）I 类α和β2 微球蛋白链在肿瘤细胞表面的缺乏，以及 Fas 和其他自然杀伤细胞免疫检查点分子的表达或可及性。相反，SM 的合成和水解越来越多地与癌症的发生和转移的促进有关。表面膜 SM 很容易形成分子间和分子内氢键网络，其过度紧密会损害细胞-细胞接触抑制、细胞内和细胞间信号、代谢途径以及对宿主免疫细胞和介质的敏感性。本综述旨在阐明肿瘤免疫逃逸机制，这些机制面临着常见的免疫治疗方法，并引起人们对与细胞表面生化变化相关的肿瘤发生的完全不同的、被忽视的关键方面的关注，这些变化导致接触抑制失败，这是一种重要的肿瘤发生机制。此外，该综述旨在为细胞膜 SM 水平及其在细胞对死亡、对生长抑制信号的反应失败和免疫逃逸的抵抗中的作用提供证据，并提出可能的癌症控制和治疗的新方法。
