决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Unravelling SLC7 family members in thyroid cancer and translational barriers.
SLC7 家族转运蛋白是一类重要的膜蛋白,可促进不同氨基酸跨细胞膜转运。
SLC7家族转运蛋白是一类重要的膜蛋白,可介导不同氨基酸跨细胞膜转运,在致癌信号通路、细胞代谢和氧化还原平衡中发挥关键作用。既往文献已阐明SLC7在乳腺癌、肝癌、前列腺癌和肺癌中的作用,但其家族成员在甲状腺癌中的功能仍不清楚。因此,本综述考察SLC7的新兴作用、甲状腺癌进展的分子机制及改善其治疗递送的策略。在甲状腺癌中,SLC7亚基突变可能进一步扰乱氨基酸代谢,并激活PI3K/AKT、mTORC1和MAPK/ERK信号通路。MYC、ATF4和HIF-1α等致癌信号的激活,可进一步提高SLC7表达,促进肿瘤进展、血管生成和细胞增殖,同时损害T细胞活化并抑制自然杀伤(NK)细胞及细胞毒性T淋巴细胞(CTL)的活性。SLC7也可作为潜在治疗靶点;采用新型免疫检查点抑制剂、工程化CAR-T细胞及CRISPR编辑细胞进行调节,是甲状腺癌治疗的有前景策略。本综述旨在阐明SLC7参与甲状腺癌发展的分子机制,识别新的治疗靶点,并改善其在甲状腺癌免疫治疗中的递送。
SLC7 family transporters are an important group of membrane proteins that facilitate the transport of different amino acids across the cell membrane. They have a crucial role in oncogenic signalling pathways, cellular metabolism, and redox balance. Previous literature had revealed the functions of SLC7 in breast, liver, prostate, and lung cancers, but the role of SLC7 family members in thyroid cancer remains unclear. Therefore, this review investigated the emerging roles of SLC7, the molecular mechanisms underlying thyroid cancer progression, and strategies to improve its therapeutic delivery. In thyroid cancer, mutations in SLC7 subunits could further dysregulate amino acid metabolism and activate the PI3K/AKT, mTORC1, and MAPK/ERK signalling pathways. The activation of oncogenic signals, such as MYC, ATF4, and HIF-1 , could further enhance the SLC7 expression by promoting tumour progression, angiogenesis, and cell proliferation, impairing T-cell activation, and inhibiting the activities of natural killer cells (NK) and cytotoxic T-lymphocytes (CTLs). They also served as potential therapeutic agents, and modulating them with novel immune checkpoint inhibitors, engineered CAR-T cells, and CRISPR-edited cells represents a promising strategy for thyroid cancer treatment. The present review could explore innovative insights into the molecular mechanisms of SLC7 in thyroid cancer development, identify the novel therapeutic targets, and improve their delivery for thyroid cancer immunotherapy.
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