Suresh P K
Department of Biomedical Sciences, School of Bio Sciences and Technology,VIT University, Vellore, Tamil Nadu, India.
J Cancer Res Ther. 2016 Oct-Dec;12(4):1224-1233. doi: 10.4103/0973-1482.176169.
Major histocompatibility complex Class I-related chain A/chain B (MICA/MICB) is stress-inducible, highly polymorphic ligands whose expression at the transcript level has been detected in all tissues except the central nervous system. However, their restricted protein expression is due to their regulation at the posttranslational level. Its levels are elevated in virally infected and neoplastically transformed cells. Membrane expression of this NKG2DL marks the aberrant cells for elimination by those immune effector cells that express the cognate NKG2D receptor. Among the evasion strategies developed by tumors, the metalloprotease-dependent shedding of MICA/MICB from tumors (either the free or the exosome form) can contribute to the inhibition of cytolysis by the immune effector cells (all NK cells, most NKT cells; γδ CD8+ T cells and αβ CD8+ T cells, as well as some αβ CD4+ T cells). There are micro-RNA clusters that regulate surface expression and shedding. Polymorphic variants can be used as susceptibility/associative markers and can also possibly be used to correlate with tumor survival as well as staging/grading of tumors. Variations in the expression level require quantification of this marker for diagnostic/prognostic and therapeutic purposes. Mechanism-based studies would provide a better tumor-specific understanding of their relative roles in the processes of tumor cell elimination versus growth and progression. Last but not least, conventional, interlaboratory validated assays (for, e.g., antibody-based methods) should be replaced by robust, reproducible, feasible biophysics-based methods using tumor biopsies. Further, correlative DNA polymorphism-based studies can be done using biological fluids (for, e.g., human saliva) that can be sampled by minimally invasive means.
主要组织相容性复合体I类相关链A/链B（MICA/MICB）是应激诱导的、高度多态的配体，除中枢神经系统外，在所有组织的转录水平均检测到其表达。然而，它们有限的蛋白质表达归因于翻译后水平的调控。在病毒感染和肿瘤转化细胞中其水平升高。这种自然杀伤细胞2D配体（NKG2DL）的膜表达标记异常细胞，以便被表达同源自然杀伤细胞2D（NKG2D）受体的免疫效应细胞清除。在肿瘤发展的逃避策略中，肿瘤中依赖金属蛋白酶的MICA/MICB脱落（游离或外泌体形式）可导致免疫效应细胞（所有自然杀伤细胞、大多数自然杀伤T细胞；γδ CD8+ T细胞和αβ CD8+ T细胞，以及一些αβ CD4+ T细胞）对细胞溶解的抑制。存在调节表面表达和脱落的微小RNA簇。多态变体可作为易感性/关联标记，也可能用于与肿瘤存活以及肿瘤分期/分级相关联。表达水平的变化需要对该标记进行定量以用于诊断/预后和治疗目的。基于机制的研究将更好地从肿瘤特异性角度理解它们在肿瘤细胞清除与生长和进展过程中的相对作用。最后但同样重要的是，传统的、经实验室间验证的检测方法（例如基于抗体的方法）应由使用肿瘤活检的强大、可重复、可行的基于生物物理学的方法取代。此外，可以使用可通过微创方式采集的生物体液（例如人唾液）进行基于DNA多态性的相关研究。
