Nanometer-scale distribution of PD-1 in the melanoma tumor microenvironment.

Colin J Comerci, Dannielle G McCarthy, Mehdi Nosrati, Kevin B Kim, Mohammed Kashani-Sabet, W E Moerner, Stanley P Leong
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Abstract

The nanometer-scale spatial organization of immune receptors plays a role in cell activation and suppression. While the connection between this spatial organization and cell signaling events is emerging from cell culture experiments, how these results translate to more physiologically relevant settings like the tumor microenvironment remains poorly understood due to the challenges of high-resolution imaging in vivo. Here we perform super-resolution immunofluorescence microscopy of human melanoma tissue sections to examine the spatial organization of the immune checkpoint inhibitor programmed cell death 1 (PD-1). We show that PD-1 exhibits a variety of organizations ranging from nanometer-scale clusters to more uniform membrane labeling. Our results demonstrate the capability of super-resolution imaging to examine the spatial organization of immune checkpoint markers in the tumor microenvironment, suggesting a future direction for both clinical and immunology research.

Abstract Image

Abstract Image

PD-1在黑色素瘤微环境中的纳米级分布。
免疫受体的纳米尺度空间组织在细胞活化和抑制中起作用。虽然这种空间组织和细胞信号事件之间的联系正在从细胞培养实验中出现,但由于体内高分辨率成像的挑战,这些结果如何转化为更生理相关的环境,如肿瘤微环境,仍然知之甚少。在这里,我们对人类黑色素瘤组织切片进行超分辨率免疫荧光显微镜检查免疫检查点抑制剂程序性细胞死亡1 (PD-1)的空间组织。我们发现PD-1表现出从纳米级簇到更均匀的膜标记的各种组织。我们的研究结果证明了超分辨率成像在肿瘤微环境中检测免疫检查点标记物空间组织的能力,为临床和免疫学研究提供了一个未来的方向。
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