间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题，原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
低剂量放疗通过促进 T 细胞浸润与 iRGD-antiCD3 修饰的 T 细胞协同作用
英文原题：Low-dose radiotherapy synergizes with iRGD-antiCD3-modified T cells by facilitating T cell infiltration.
查看英文原题
Low-dose radiotherapy synergizes with iRGD-antiCD3-modified T cells by facilitating T cell infiltration.
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研究概要
我们证明了低剂量放疗可通过促进 T 细胞浸润来增强 iRGD-antiCD3 修饰 T 细胞的抗肿瘤效力，为在实体瘤中探索低剂量放疗与其他过继性 T 细胞疗法的联合应用提供了依据。
研究思路结论见上方概要
背景
转染T细胞浸润不良是阻碍实体瘤过继细胞治疗发展的关键因素。我们在前期工作中证明iRGD-antiCD3修饰可促进T细胞浸润和活化。近年来，低剂量放疗因其包括T细胞募集在内的免疫刺激效应而重新受到关注。本研究旨在探讨低剂量放疗与iRGD-antiCD3修饰T细胞之间的协同效应。
方法
进行流式细胞术以评估iRGD受体和趋化因子的表达。通过免疫组织荧光和体内实时荧光成像评估T细胞浸润，并在胃癌腹膜转移小鼠模型中通过体内生物发光成像研究抗肿瘤效果。
结果
我们发现2 Gy照射上调了所有三种iRGD受体和T细胞趋化因子的表达。加入2 Gy低剂量照射促进了iRGD-antiCD3修饰T细胞在腹膜肿瘤结节中的聚集和穿透。将2 Gy低剂量照射与iRGD-antiCD3修饰T细胞联合使用，在腹膜转移小鼠模型中显著抑制了肿瘤生长并延长了生存期，且安全性良好。
展开英文摘要原文
MATERIALS AND METHODS
Flow cytometry was performed to assess the expression of iRGD receptors and chemokines. T cell infiltration was evaluated by immunohistofluorescence and in vivo real-time fluorescence imaging and antitumor effects were investigated by in vivo bioluminescence imaging in the gastric cancer peritoneal metastasis mouse model.
RESULTS
We found that 2 Gy irradiation upregulated the expression of all three iRGD receptors and T-cell chemokines. The addition of 2 Gy low-dose irradiation boosted the accumulation and penetration of iRGD-antiCD3-modified T cells in peritoneal tumor nodules. Combining 2 Gy low-dose irradiation with iRGD-antiCD3-modified T cells significantly inhibited tumor growth and prolonged survival in the peritoneal metastasis mouse model with a favorable safety profile.
CONCLUSION
Altogether, we demonstrated that low-dose radiotherapy could improve the antitumor potency of iRGD-antiCD3-modified T cells by promoting T cell infiltration, providing a rationale for exploring low-dose radiotherapy in combination of other adoptive T cell therapies in solid tumors.
论文信息
- 作者
- Zhou S、Zhu M、Wei X、Mu P、Shen L、Wang Y、Wan J、Zhang H
- 第一作者单位
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai 200032, China; Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China.China
- 通讯作者单位
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai 200032, China; Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China. Electronic address: zhen_zhang@fudan.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2024 May
- 原文标识
- PubMed 38458258 · DOI 10.1016/j.radonc.2024.110213