免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Neo-Splicetopes in Tumor Therapy: A Lost Case?
Neo-Splicetopes in Tumor Therapy: A Lost Case?
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蛋白酶体通过反向蛋白水解反应连接两个相距较远的切割产物,从而生成剪接肽。在一名黑色素瘤患者中,识别剪接肽的 CD8+ T 细胞在过继性 T 细胞转移(ATT)后诱导了 T 细胞排斥反应,这一观察结果引发了人们对剪接肽在治疗和免疫方面普遍相关性的期待。与此同时,剪接肽的鉴定也开启了一场关于其频率、丰度及治疗适用性的争议。在此,我综述一些近期支持或反对剪接表位免疫相关性的证据,并从理论角度讨论肿瘤特异性剪接表位的潜在用途,以及为何尽管困难重重,鉴定此类肿瘤和患者特异性新剪接表位用于 ATT 仍可能值得尝试。
Proteasome generates spliced peptides by ligating two distant cleavage products in a reverse proteolysis reaction. The observation that CD8+ T cells recognizing a spliced peptide induced T cell rejection in a melanoma patient following adoptive T cell transfer (ATT), raised some hopes with regard to the general therapeutic and immune relevance of spliced peptides. Concomitantly, the identification of spliced peptides was also the start of a controversy with respect to their frequency, abundancy and their therapeutic applicability.
Here I review some of the recent evidence favoring or disfavoring an immune relevance of splicetopes and discuss from a theoretical point of view the potential usefulness of tumor specific splicetopes and why against all odds it still may seem worth trying to identify such tumor and patient-specific neosplicetopes for application in ATT.
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