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首页> 外文期刊>Journal of Cellular Physiology >T11TS immunotherapy repairs PI3K‐AKT signaling in T‐cells: Clues toward enhanced T‐cell survival in rat glioma model
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T11TS immunotherapy repairs PI3K‐AKT signaling in T‐cells: Clues toward enhanced T‐cell survival in rat glioma model

机译:T11TS免疫疗法修复PI3K公/ AKT信号T细胞:应承担的线索对增强T细胞生存大鼠神经胶质瘤模型

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Malignant glioma is the most fatal of astrocytic lineage tumors despite therapeutic advances. Onset and progression of gliomas is accompanied by severe debilitation of T‐cell defense and T‐cell survival. One of the chief contributors to T‐cell survival downstream of activation is the PI3K‐AKT pathway. Our prior studies showed that the novel immunotherapeutic molecule T11‐target structure (T11TS) blocks T‐cell apoptosis in glioma. We also showed activation of immunological synapse components and calcineurin‐NFAT pathway following T11TS immunotherapy of glioma‐bearing rats. This lead to investigations whether such T‐cell activation upon T11TS therapy translates into activation of downstream PI3K/AKT signals which may be related to observed blockade of T‐cell apoptosis. For the purpose, we assessed by flowcytometry and immunoblotting, expressions of PI3K, PDK1, AKT, p‐AKT, and PTEN in splenic T‐cells of normal, experimentally‐induced glioma‐bearing rats and glioma‐bearing rats receiving first, second and third doses of T11TS. We also determined comparative nuclear translocation of NF‐κB across groups. We found significant increases in T‐cell expressions of PDK1, PI3K, and p‐AKT in T11TS‐treated animal groups compared to sharp downregulations in glioma. AKT levels remained unchanged across groups. PTEN levels declined sharply after T11TS immunotherapy. T11TS also caused enhanced NF‐κB translocation to the T‐cell nucleus compared to glioma group. Results showed heightened activation of the PI3K‐AKT pathway in glioma‐bearing rats following T11TS immunotherapy. These results illustrate the novel role of T11TS immunotherapy in ameliorating the PI3K pathway in T‐cells in glioma‐bearing animals to enhance T‐cell survival, according greater defense against glioma. The study thus has far‐reaching clinical outcomes.
机译:恶性神经胶质瘤是最致命的病患尽管家族肿瘤治疗进展。神经胶质瘤的发病和进展是陪同严重衰弱的T细胞防御T细胞的生存。量T细胞激活的下游是生存PI3K AKT通路。新型免疫治疗分子T11的目标结构(T11TS)阻断T细胞凋亡神经胶质瘤。免疫突触的组件和钙调磷酸酶T11TS后NFAT通路神经胶质瘤免疫治疗的老鼠必经轴承。调查是否这些T细胞的激活在T11TS疗法转化为激活下游PI3K / AKT信号可能是相关的观察到的封锁T细胞凋亡。目的,我们通过flowcytometry和评估PI3K的表达,免疫印迹基因,一种蛋白激酶,p量AKT, PTEN在脾T细胞正常的,应承担的实验检测诱导神经胶质瘤的老鼠和轴承神经胶质瘤列车轴承老鼠接收第一,第二第三剂T11TS。地理比较核易位NFκB组。基因的表达、PI3K和p AKT在T11TS优先对待动物组织而尖锐downregulations神经胶质瘤。跨组织不变。大幅T11TS免疫治疗后。导致增强NFκB易位应承担的T细胞核相比,神经胶质瘤组。加剧了PI3K量AKT通路的激活神经胶质瘤T11TS后轴承的老鼠免疫疗法。T11TS免疫疗法在改善的作用PI3K通路在T细胞在神经胶质瘤轴承应承担的动物增强T细胞生存,应承担更大神经胶质瘤防御。量达到临床结果。

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