免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Mapping the single cell spatial immune landscapes of the melanoma microenvironment.
Mapping the single cell spatial immune landscapes of the melanoma microenvironment.
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黑色素瘤是一种高度免疫原性的恶性肿瘤,具有较高的突变负荷、弥漫性淋巴细胞浸润,并且是对免疫检查点抑制剂(ICIs)缓解率最高的肿瘤之一。
然而,在接受ICIs治疗的所有晚期患者中,超过半数要么无应答,要么出现疾病进展。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)。此类研究的目标是理解基质、黑色素瘤细胞和免疫细胞类型之间复杂的相互作用,以及它们与治疗应答的关联。寻求更好地理解细胞在TME中位置的作用以及生物标志物空间表达重要性的研究者,正越来越多地转向高度多重成像方法,以更准确地测量免疫浸润,并量化受体-配体相互作用(如PD-1和PD-L1)以及细胞间接触。CyTOF-IMC(飞行时间流式细胞术-成像质谱流式细胞术)已使黑色素瘤的高维图谱分析成为可能,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,已揭示了免疫细胞浸润的独特模式,凸显了空间关系的重要性及其对调节免疫治疗应答的影响。
总体而言,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,为生物标志物发现和治疗开发提供了新途径。这些技术为推进个性化医疗以改善黑色素瘤和其他实体恶性肿瘤患者的预后带来了巨大希望。
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.
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