不可逆电穿孔增强 CAR-T 细胞对实体瘤的浸润与选择性癌细胞裂解
Irreversible Electroporation Enhances Solid Tumor Infiltration and Selective Cancer Cell Lysis by CAR T Cells.
通过利用一种双用途转化策略——直接的癌细胞靶向细胞毒性和增强的 CAR-T 细胞浸润——sIRE 能够减轻肿瘤负荷，同时保持并增强 CAR-T 细胞功能。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
肿瘤内免疫三联体是免疫治疗介导的实体瘤消除所必需的
英文原题：Intratumoral immune triads are required for immunotherapy-mediated elimination of solid tumors.
查看英文原题
Intratumoral immune triads are required for immunotherapy-mediated elimination of solid tumors.
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中文摘要
肿瘤特异性CD8+ T细胞常功能失调，无法阻止肿瘤生长。我们研究了肿瘤特异性CD4+ T细胞能否被调动以克服肿瘤内CD8+ T细胞的功能障碍。我们发现，在过继性T细胞治疗以及免疫检查点阻断（ICB）的背景下，CD8+和CD4+ T细胞的空间定位和相互作用，而非其数量，决定了抗肿瘤反应：CD4+ T细胞必须在效应阶段与同一个树突状细胞上的CD8+ T细胞相互作用，形成三细胞型簇（三联体），从而赋予CD8+ T细胞细胞毒性和癌细胞清除能力。当瘤内三联体形成被破坏时，尽管肿瘤特异性CD8+和CD4+ T细胞数量相等，肿瘤仍会进展。在接受ICB治疗的胸膜间皮瘤患者中，三联体与临床反应相关。因此，在效应阶段，CD4+ T细胞和三联体是CD8+ T细胞细胞毒性和肿瘤清除所必需的。
展开英文摘要原文
Tumor-specific CD8 + T cells are frequently dysfunctional and unable to halt tumor growth.
We investigated whether tumor-specific CD4 + T cells can be enlisted to overcome CD8 + T cell dysfunction within tumors.
We find that the spatial positioning and interactions of CD8 + and CD4 + T cells, but not their numbers, dictate anti-tumor responses in the context of adoptive T cell therapy as well as immune checkpoint blockade (ICB): CD4 + T cells must engage with CD8 + T cells on the same dendritic cell during the effector phase, forming a three-cell-type cluster (triad) to license CD8 + T cell cytotoxicity and cancer cell elimination.
When intratumoral triad formation is disrupted, tumors progress despite equal numbers of tumor-specific CD8 + and CD4 + T cells. In patients with pleural mesothelioma treated with ICB, triads are associated with clinical responses.
Thus, CD4 + T cells and triads are required for CD8 + T cell cytotoxicity during the effector phase and tumor elimination.
论文信息
- 作者
- Espinosa-Carrasco G、Chiu E、Scrivo A、Zumbo P、Dave A、Betel D、Kang SW、Jang HJ
- 第一作者单位
- Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: gespinosa@idibell.cat.United States
- 通讯作者单位
- Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA. Electronic address: schietia@mskcc.org.United States
- 文献类型
- 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Cancer cell2024 Jul 8
- 原文标识
- PubMed 38906155 · DOI 10.1016/j.ccell.2024.05.025
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