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
离体扩增的肿瘤抗原致敏细胞毒性 T 细胞对恶性黑色素瘤的抗肿瘤活性
英文原题：Antitumor Activity of Ex Vivo Expanded Tumor Antigen Priming Cytotoxic T Cells Against Malignant Melanoma.
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Antitumor Activity of Ex Vivo Expanded Tumor Antigen Priming Cytotoxic T Cells Against Malignant Melanoma.
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研究概要
用灭活的同种异体黑色素瘤细胞致敏的 DC 能有效交叉致敏特异性靶向 Melan-A 抗原的细胞毒性 T 细胞。此外，经 Melan-A 负载 DC 致敏的初始 CD8+ T 细胞成功杀死了恶性黑色素瘤细胞，凸显了其作为一种针对黑色素瘤的过继性免疫治疗策略的前景。
研究思路结论见上方概要
背景
树突状细胞（DCs）能够从组织中捕获抗原并迁移至淋巴结，在此通过主要组织相容性复合体（MHC）I 将细胞相关抗原交叉提呈给分化簇（CD）8+ T 细胞。细胞毒性 T 淋巴细胞通过 T 细胞受体识别由 MHC I/β2-微球蛋白复合体呈现在癌细胞表面的特异性肽段，从而清除恶性细胞。本研究旨在探讨体外扩增的、经肿瘤抗原致敏的细胞毒性 T 细胞对恶性黑色素瘤的抗肿瘤活性。
方法
T细胞通过DC-T细胞共培养和外周血单个核细胞（PBMC）方法诱导，分别在有或无Melan-A/MART-1肽刺激的条件下进行。使用Melan-A链霉亲和素多聚体进行T细胞分析。在第1周和第2周测量干扰素-γ和颗粒酶B的分泌水平。分析T细胞亚型，并评估对黑色素瘤细胞的细胞毒性活性。
结果
阳性斑点数量随时间显著增加。CD4 + 和 CD8 + T 细胞扩增，且 CD4 + T 细胞是优势 T 细胞亚型。肿瘤细胞（SK-MEL-28）数量随细胞毒性 T 淋巴细胞:T 比例升高而减少。共培养后立即观察到细胞毒性，并在 72 h 内逐渐增强。
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MATERIALS AND METHODS
T cells were induced using DC-T cell coculture and peripheral blood mononuclear cell (PBMC) methods, with and without Melan-A/MART-1 peptide stimulation. Melan-A streptamers were used for T-cell analysis. Interferon-γ and granzyme B secretion levels were measured at 1 and 2 weeks. T-cell subtypes were analyzed, and cytotoxic activity against melanoma cells was evaluated.
RESULTS
The number of positive spots significantly increased over time. CD4 + and CD8 + T cells expanded, and CD4 + T cells were the dominant T-cell subtype. The number of tumor cells (SK-MEL-28) decreased according to the cytotoxic T lymphocyte:T ratio. Cytotoxicity was observed immediately after coculture and gradually increased over 72 h.
CONCLUSION
DCs pulsed with killed allogeneic melanoma cells effectively cross-prime cytotoxic T cells that specifically target the Melan-A antigen. Moreover, naive CD8 + T cells primed by Melan-A-loaded DCs successfully killed malignant melanoma cells, highlighting a promising strategy for adoptive immunotherapy against melanoma.
论文信息
- 作者
- Yoon HS、Park YG、Cho DY、Kim JS、Choi JG
- 第一作者单位
- Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, Republic of Korea.South Korea
- 通讯作者单位
- Department of Hemato-Oncology, Konyang University Hospital, Daejeon, Republic of Korea jabuss@naver.com.South Korea
- 期刊
- Anticancer research2025 Jun
- 原文标识
- PubMed 40425324 · DOI 10.21873/anticanres.17607