Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada.
Department of Human Genetics, McGill University, Montréal, QC, Canada.
Clin Exp Metastasis. 2024 Aug;41(4):301-312. doi: 10.1007/s10585-023-10252-4. Epub 2024 Jan 13.
Melanoma is a highly immunogenic malignancy with an elevated mutational burden, diffuse lymphocytic infiltration, and one of the highest response rates to immune checkpoint inhibitors (ICIs). However, over half of all late-stage patients treated with ICIs will either not respond or develop progressive disease. Spatial imaging technologies are being increasingly used to study the melanoma tumor microenvironment (TME). The goal of such studies is to understand the complex interplay between the stroma, melanoma cells, and immune cell-types as well as their association with treatment response. Investigators seeking a better understanding of the role of cell location within the TME and the importance of spatial expression of biomarkers are increasingly turning to highly multiplexed imaging approaches to more accurately measure immune infiltration as well as to quantify receptor-ligand interactions (such as PD-1 and PD-L1) and cell-cell contacts. CyTOF-IMC (Cytometry by Time of Flight - Imaging Mass Cytometry) has enabled high-dimensional profiling of melanomas, allowing researchers to identify complex cellular subpopulations and immune cell interactions with unprecedented resolution. Other spatial imaging technologies, such as multiplexed immunofluorescence and spatial transcriptomics, have revealed distinct patterns of immune cell infiltration, highlighting the importance of spatial relationships, and their impact in modulating immunotherapy responses. Overall, spatial imaging technologies are just beginning to transform our understanding of melanoma biology, providing new avenues for biomarker discovery and therapeutic development. These technologies hold great promise for advancing personalized medicine to improve patient outcomes in melanoma and other solid malignancies.
黑色素瘤是一种高度免疫原性的恶性肿瘤，具有较高的突变负担、弥漫性淋巴细胞浸润，并且对免疫检查点抑制剂（ICIs）的反应率最高之一。然而，超过一半接受 ICI 治疗的所有晚期患者要么没有反应，要么发展为进行性疾病。空间成像技术正越来越多地用于研究黑色素瘤肿瘤微环境（TME）。此类研究的目的是了解基质、黑色素瘤细胞和免疫细胞类型之间的复杂相互作用，以及它们与治疗反应的关系。研究人员越来越希望更好地了解细胞在 TME 中的位置以及生物标志物空间表达的重要性，因此他们越来越多地转向高度多重化的成像方法，以更准确地测量免疫浸润，以及量化受体-配体相互作用（如 PD-1 和 PD-L1）和细胞-细胞接触。CyTOF-IMC（飞行时间 - 成像质谱流式细胞术）使黑色素瘤的高维分析成为可能，使研究人员能够以前所未有的分辨率识别复杂的细胞亚群和免疫细胞相互作用。其他空间成像技术，如多重免疫荧光和空间转录组学，揭示了免疫细胞浸润的不同模式，强调了空间关系的重要性及其在调节免疫治疗反应中的作用。总的来说，空间成像技术才刚刚开始改变我们对黑色素瘤生物学的理解，为生物标志物的发现和治疗开发提供了新的途径。这些技术为推进个性化医疗提供了巨大的潜力，以改善黑色素瘤和其他实体恶性肿瘤患者的治疗效果。
