RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:A comparative study of carbonic anhydrase activity in lymphocytes from colorectal cancer tissues and adjacent healthy counterparts.
A comparative study of carbonic anhydrase activity in lymphocytes from colorectal cancer tissues and adjacent healthy counterparts.
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多种碳酸酐酶(CA,EC 4.2.1.1)亚型参与肿瘤发生相关过程,可高效催化二氧化碳水合生成碳酸氢根和质子。CA IX 和 CA XII 等亚型已被证实在许多实体瘤中上调。另一方面,癌症与免疫系统密切相关,近期研究显示靶向免疫检查点可有效改善恶性肿瘤治疗。本研究调查了TIL(肿瘤浸润淋巴细胞)中 CA 亚型的表达;根据免疫监视理论,TIL 在结直肠癌(CRC)发生中可能发挥关键作用。从健康邻近黏膜分离的 T 淋巴细胞,其 CA 活性高于同一患者肿瘤组织和外周血中的 T 细胞。对相应 TIL 样本进行蛋白质组分析后,确认 CA I 和 CA II 是参与该过程的酶亚型。这些初步发现提示 CRC 组织局部免疫反应失调,且 CA 介导的有效抗癌机制有所丧失。
Several carbonic anhydrase (CA, EC 4. 2. 1. 1) isoforms play an essential role in processes connected to tumorigenesis, as they efficiently accelerate the hydration of carbon dioxide to bicarbonate and proton. In this context, examples are CA IX and CA XII, which were proved to be upregulated in many solid malignancies. On the other hand, cancer and the immune system are inextricably linked, and targeting the immune checkpoints recently was shown to efficiently improve the treatment of malignancies.
In this study, we have investigated the expression of CA isoforms in tumour-infiltrating lymphocytes (TILs) that, according to the immunosurveillance theory, were suggested to have a crucial role in the development of colorectal cancer (CRC). T lymphocytes isolated from healthy surrounding mucosa showed a higher CA activity compared to those present in tumour and peripheral blood in the same patients.
CA I and II were confirmed as enzyme isoforms involved in the process, as determined by proteomic analysis of corresponding TIL samples. These preliminary findings suggest a dysregulation of the local immune response in the CRC tissues and a loss of effective anticancer mechanisms mediated by CAs therein.
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