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光磁成像用于优化乳腺癌中淋巴细胞清除-TIL 联合治疗

英文原题:Optical-magnetic Imaging for Optimizing Lymphodepletion-TIL Combination Therapy in Breast Cancer.

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Optical-magnetic Imaging for Optimizing Lymphodepletion-TIL Combination Therapy in Breast Cancer.

PubMed 2025/02/05(内容时间) Mol Imaging Biol Q2 · IF 2.5(JCR 2025)

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研究概要

我们的结果证实了光学-磁双模态成像在追踪 TIL 体内生物分布方面的实用性。借助光学-磁双模态成像,我们成功优化了 TIL 联合治疗。光学-磁双模态成像为开发个性化免疫治疗策略和挖掘 TIL 潜在治疗机制提供了新途径。

研究思路结论见上方概要

TIL(肿瘤浸润淋巴细胞)输注前的淋巴细胞清除可以激活免疫系统,增强稳态细胞因子的释放,并减少免疫抑制细胞的数量。这一过程对于提高TIL治疗的疗效至关重要。然而,体内评估靶向肿瘤的TILs的挑战限制了淋巴细胞清除预处理方案(LDC)的优化。方法:本研究旨在采用磁粒子成像(MPI)和荧光分子成像(FMI)监测TIL在体内的生物分布,并优化三阴性乳腺癌TIL治疗中的LDC。MPI提供无深度限制的定量成像能力,有效补充了FMI的高灵敏度。使用FMI评估不同LDC在增强TIL治疗中的疗效,MPI量化了在4T1肿瘤中积累的TIL数量。

TIL经超顺磁性氧化铁和荧光染料DiR标记后,其活力、表型及抗肿瘤疗效均得以保留。双模态成像系统有效识别了增强TIL治疗的LDC处理差异。与TIL单一疗法相比,淋巴细胞清除联合TIL治疗提高了肿瘤双模态成像信号强度,增加了血清和肿瘤组织中单核细胞趋化蛋白-1的表达,并增强了TIL的治疗效果。

展开英文摘要原文

Lymphodepletion before tumor-infiltrating lymphocytes (TIL) infusion can activate the immune system, enhance the release of homeostatic cytokines, and decrease the number of immunosuppressive cells. This process is crucial for improving the therapeutic efficacy of TIL therapy. However, the challenge of in vivo assessing TILs targeting tumors limits the optimization of lymphodepleting conditioning regimen (LDC). PROCEDURES: This study aims to employ magnetic particle imaging (MPI) and fluorescence molecular imaging (FMI) to monitor TIL biodistribution in vivo and optimize LDC in triple-negative breast cancer TIL therapy. MPI provides quantitative imaging capabilities without depth limitations, effectively complementing the high sensitivity of FMI. The efficacy of different LDCs in enhancing TIL therapy was assessed using FMI, and MPI quantified the number of TILs accumulated in the 4T1 tumor.

TILs preserved viability, phenotypes, and anti-tumor efficacy after being labeled with superparamagnetic iron oxide and fluorescence dye DiR. The dual-modality imaging system effectively discerned variations in LDC treatments that enhanced TIL therapy. Compared to TIL monotherapy, lymphodepletion with TIL therapy improves tumor dual-modality imaging signal intensity, increases the expression of monocyte chemotactic protein-1 in serum and tumor tissue, and enhances the therapeutic effect of TILs.

Our results confirm the utility of optical-magnetic dual-modality imaging for tracking the biodistribution of TILs in vivo. With the help of optical-magnetic dual-modality imaging, we successfully optimize TIL combination therapy. Optical-magnetic dual-modality imaging provides a new approach to develop personalized immunotherapy strategies and mine potential therapeutic mechanisms for TIL.

论文信息

作者
Li J、Guo L、Feng Y、Li G、Sun H、Huang W、Tian J、Du Y
第一作者单位
School of Engineering Medicine & School of Biological Science and Medicine Engineering, Beihang University, Beijing, 100191, China.China
通讯作者单位
School of Engineering Medicine & School of Biological Science and Medicine Engineering, Beihang University, Beijing, 100191, China. yuan1989@buaa.edu.cn.China
期刊
Molecular imaging and biology2025 Apr
原文标识
PubMed 39909989 · DOI 10.1007/s11307-025-01985-7