癌细胞表达的免疫球蛋白在癌症免疫学中的双重作用

Gregory Lee, Cheng-Yuan Huang, S. Liu, C. Chien, S. Chow
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引用次数: 6

摘要

虽然免疫球蛋白和T细胞受体在癌细胞上的表达已经建立了几十年,但这些癌性抗原受体的潜在作用和作用机制尚未完全阐明。一种被命名为RP215的单克隆抗体,可以与位于癌性免疫球蛋白和T细胞受体重链区域的糖相关表位发生特异性反应,作为一种独特的探针来研究抗原受体在癌细胞免疫学中的作用。通过广泛的基于细胞的生物学和免疫学研究,发现抗抗原受体和RP215对参与癌细胞生长/增殖的基因调控以及参与先天免疫的toll样受体的作用相似。此外,rp215特异性癌性免疫球蛋白被认为可以捕获或中和可能对人体内癌细胞有害的循环抗原/抗体。与常规免疫系统中正常的B细胞和T细胞及其受体不同,癌细胞同时表达免疫球蛋白和T细胞受体,免疫保护通过独特的机制发挥作用。例如,这些癌细胞表达的抗原受体表现出缺乏类转换、有限的超突变、异常的糖基化和对癌细胞的toll样受体的强烈影响。因此,假设正常免疫系统和癌变免疫系统可能在人体内共存并同时运作。这两种免疫因子在各自的监测和保护方面的平衡可能与人类癌症免疫治疗的结果有关。基于这些观察结果,人们正在开发一种潜在的治疗策略,即使用RP215作为靶向癌细胞的候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
DUAL ROLES OF CANCER CELL-EXPRESSED IMMUNOGLOBULINS IN CANCER IMMUNOLOGY
While the expression of immunoglobulins and T cell receptors on cancer cells has been well-established for decades, the potential roles and mechanisms of action of these cancerous antigen receptors have not been fully elucidated. A monoclonal antibody designated as RP215, which reacts specifically with the carbohydrate-associated epitope located on the heavy chain region of cancerous immunoglobulins and T cell receptors, was used as a unique probe to study the roles of antigen receptors in the immunology of cancer cells. Through extensive cell-based biological and immunological studies, it was found that both anti-antigen receptors and RP215 demonstrated similar actions on the gene regulations involved in the growth/proliferation of cancer cells, as well as on toll-like receptors involved in innate immunity. In addition, RP215-specific cancerous immunoglobulins are believed to capture or neutralize circulating antigen/antibodies which may be harmful to cancer cells within the human body. In contrast to normal B and T cells and their respective receptors in the conventional immune system, cancer cells co-express both immunoglobulins and T cell receptors and immune protection is exercised by unique mechanisms. For example, these cancer cell-expressed antigen receptors display a lack of class switching, limited hyper-mutation, aberrant glycosylations and a strong influence on the toll-like receptors of cancer cells. Therefore, it is hypothesized that both normal and cancerous immune systems may co-exist and operate simultaneously within the human body. The balance of these two immune factors for respective surveillance and protection may be relevant to the outcome of cancer immunotherapy in humans. A potential therapeutic strategy is being developed by using RP215 as a drug candidate to target cancer cells based on these observations.
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