Longitudinal imaging of T cell-based immunotherapy with multi-spectral, multi-scale optoacoustic tomography
Longitudinal imaging of T cell-based immunotherapy with multi-spectral, multi-scale optoacoustic tomography
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DOI：
10.1038/s41598-020-61191-z
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发表时间：
2020-03-17
影响因子：
4.6
通讯作者：
Ntziachristos，Vasilis
中科院分区：
文献类型：
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作者：
Kimm，Melanie A.;Tzoumas，Stratis;Ntziachristos，Vasilis
大多数免疫治疗的成像研究都集中在追踪标记的T细胞在体内的生物分布，以了解运输和归巢参数，并通过肿瘤块中转移的T细胞的存在来预测治疗效果。相反，我们在这里研究了一种新的概念，用于纵向阐明在临床前设置中过继性T细胞转移后实体瘤的解剖学和病理生理学变化，使用先前未探索的串联宏观和介观光声（光声）成像。我们显示了在整个肿瘤的肿瘤排斥过程中血管塌陷的非侵入性活体观察，并首次观察到纵向肿瘤排斥反应，该排斥反应是基于肿瘤质量中由于细胞衰退而引起的光学吸收变化。我们补充了这些观察与高分辨率episcopic荧光成像的T细胞生物分布使用优化的T细胞标记的基础上，两个近红外染料靶向细胞膜和细胞质。我们讨论了如何光声宏观和介观提供独特的对比度和免疫治疗的见解，允许无标记和纵向观察肿瘤治疗。结果表明，光声成像是理解和优化T细胞治疗的宝贵工具。
Most imaging studies of immunotherapy have focused on tracking labeled T cell biodistributionin vivofor understanding trafficking and homing parameters and predicting therapeutic efficacy by the presence of transferred T cells at or in the tumour mass. Conversely, we investigate here a novel concept for longitudinally elucidating anatomical and pathophysiological changes of solid tumours after adoptive T cell transfer in a preclinical set up, using previously unexplored in-tandem macroscopic and mesoscopic optoacoustic (photoacoustic) imaging. We show non-invasivein vivoobservations of vessel collapse during tumour rejection across entire tumours and observe for the first time longitudinal tumour rejection in a label-free manner based on optical absorption changes in the tumour mass due to cellular decline. We complement these observations with high resolution episcopic fluorescence imaging of T cell biodistribution using optimized T cell labeling based on two near-infrared dyes targeting the cell membrane and the cytoplasm. We discuss how optoacoustic macroscopy and mesoscopy offer unique contrast and immunotherapy insights, allowing label-free and longitudinal observations of tumour therapy. The results demonstrate optoacoustic imaging as an invaluable tool in understanding and optimizing T cell therapy.