Spatially mapping the immune landscape of melanoma using imaging mass cytometry
Spatially mapping the immune landscape of melanoma using imaging mass cytometry
复制标题
利用成像细胞术绘制黑色素瘤免疫景观的空间图
DOI：
10.1126/sciimmunol.abi5072
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发表时间：
2022-04-01
影响因子：
24.8
通讯作者：
Watson, Ian R.
中科院分区：
文献类型：
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作者：
Moldoveanu, Dan;Ramsay, LeeAnn;Watson, Ian R.
黑色素瘤是一种免疫原性癌症，对免疫检查点抑制剂（ICIs）有很高的应答率。与其他癌症相比，它具有较高的突变负担，因此在其微环境中具有丰富的肿瘤浸润淋巴细胞（til）。然而，了解基质、肿瘤细胞和不同TIL亚群之间复杂的相互作用仍然是免疫肿瘤学的一个重大挑战。为了正确研究这种相互作用，量化肿瘤微环境中多种细胞类型的空间关系至关重要。为了解决这个问题，我们使用细胞术飞行时间（CyTOF）成像质量细胞术（IMC）同时量化35个蛋白标志物的表达，表征5个良性痣和67个黑色素瘤的微环境。我们分析了超过22万个个体细胞，以鉴定黑色素瘤、淋巴细胞亚群、巨噬细胞/单核细胞和基质细胞群，从而对黑色素瘤微环境进行深入的空间量化。我们发现，在预处理黑色素瘤中，增殖抗原经历的细胞毒性T细胞(CD8(+)CD45RO（+)Ki67(+)）的丰度以及抗原经历的细胞毒性T细胞与黑色素瘤细胞的接近度与ICIs的阳性反应相关。我们的研究强调了多重单细胞技术在量化肿瘤微环境中空间细胞-细胞相互作用以了解免疫治疗反应方面的潜力。
Melanoma is an immunogenic cancer with a high response rate to immune checkpoint inhibitors (ICIs). It harbors a high mutation burden compared with other cancers and, as a result, has abundant tumor-infiltrating lymphocytes (TILs) within its microenvironment. However, understanding the complex interplay between the stroma, tumor cells, and distinct TIL subsets remains a substantial challenge in immune oncology. To properly study this interplay, quantifying spatial relationships of multiple cell types within the tumor microenvironment is crucial. To address this, we used cytometry time-of-flight (CyTOF) imaging mass cytometry (IMC) to simultaneously quantify the expression of 35 protein markers, characterizing the microenvironment of 5 benign nevi and 67 melanomas. We profiled more than 220,000 individual cells to identify melanoma, lymphocyte subsets, macrophage/monocyte, and stromal cell populations, allowing for in-depth spatial quantification of the melanoma microenvironment. We found that within pretreatment melanomas, the abundance of proliferating antigen-experienced cytotoxic T cells (CD8(+)CD45RO(+)Ki67(+)) and the proximity of antigen-experienced cytotoxic T cells to melanoma cells were associated with positive response to ICIs. Our study highlights the potential of multiplexed single-cell technology to quantify spatial cell-cell interactions within the tumor microenvironment to understand immune therapy responses.