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
单个 T 细胞受体在成功癌症免疫治疗中对多种肿瘤相关抗原的靶向
英文原题：Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy.
查看英文原题
Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy.
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中文摘要
免疫系统的T细胞能够在TIL（肿瘤浸润淋巴细胞）治疗后靶向肿瘤并清除实体癌。我们利用组合肽文库和蛋白质组数据库，揭示了在IV期恶性黑色素瘤TIL治疗成功后持续性癌症特异性T细胞受体（TCR）的抗原特异性。值得注意的是，单个TCR可通过HLA A 02:01限制性表位EAAGIGILTV、LLLGIGILVL和NLSALGIFST分别靶向多种不同的肿瘤类型，这些表位分别来自Melan A、BST2和IMP2。一个TCR与全部三种抗原结合的原子结构揭示了共享的x-x-x-A/G-I/L-G-I-x-x-x识别基序的重要性。多表位靶向使单个T细胞能够同时以多种方式攻击癌症。与常规T细胞对单个表位的识别相比，这种“多管齐下”的T细胞对癌细胞的识别表现出优越性，使其成为未来免疫疗法开发中有吸引力的候选者。
展开英文摘要原文
The T cells of the immune system can target tumors and clear solid cancers following tumor-infiltrating lymphocyte (TIL) therapy.
We used combinatorial peptide libraries and a proteomic database to reveal the antigen specificities of persistent cancer-specific T cell receptors (TCRs) following successful TIL therapy for stage IV malignant melanoma. Remarkably, individual TCRs could target multiple different tumor types via the HLA A 02:01-restricted epitopes EAAGIGILTV, LLLGIGILVL, and NLSALGIFST from Melan A, BST2, and IMP2, respectively.
Atomic structures of a TCR bound to all three antigens revealed the importance of the shared x-x-x-A/G-I/L-G-I-x-x-x recognition motif. Multi-epitope targeting allows individual T cells to attack cancer in several ways simultaneously. Such "multipronged" T cells exhibited superior recognition of cancer cells compared with conventional T cell recognition of individual epitopes, making them attractive candidates for the development of future immunotherapies.
论文信息
- 作者
- Dolton G、Rius C、Wall A、Szomolay B、Bianchi V、Galloway SAE、Hasan MS、Morin T
- 第一作者单位
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales CF14 4XN, UK.United Kingdom
- 通讯作者单位
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales CF14 4XN, UK; Systems Immunology Research Institute, Cardiff, Wales CF14 4XN, UK. Electronic address: sewellak@cardiff.ac.uk.United Kingdom
- 文献类型
- 非美国政府资助研究
- 期刊
- Cell2023 Aug 3
- 原文标识
- PubMed 37490916 · DOI 10.1016/j.cell.2023.06.020