The Mark Foundation Center for Advanced Genomics and Imaging, Johns Hopkins University, Baltimore, MD 21287, USA.
Bloomberg~Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Science. 2021 Jun 11;372(6547). doi: 10.1126/science.aba2609.
Next-generation tissue-based biomarkers for immunotherapy will likely include the simultaneous analysis of multiple cell types and their spatial interactions, as well as distinct expression patterns of immunoregulatory molecules. Here, we introduce a comprehensive platform for multispectral imaging and mapping of multiple parameters in tumor tissue sections with high-fidelity single-cell resolution. Image analysis and data handling components were drawn from the field of astronomy. Using this "AstroPath" whole-slide platform and only six markers, we identified key features in pretreatment melanoma specimens that predicted response to anti-programmed cell death-1 (PD-1)-based therapy, including CD163PD-L1 myeloid cells and CD8FoxP3PD-1 T cells. These features were combined to stratify long-term survival after anti-PD-1 blockade. This signature was validated in an independent cohort of patients with melanoma from a different institution.
下一代基于组织的免疫疗法生物标志物可能包括同时分析多种细胞类型及其空间相互作用,以及免疫调节分子的独特表达模式。在这里,我们介绍了一种用于高保真单细胞分辨率的肿瘤组织切片中多参数的多光谱成像和映射的综合平台。图像分析和数据处理组件来自天文学领域。使用这种“天文病理”全切片平台和仅 6 种标志物,我们在预处理黑色素瘤标本中鉴定出了预测对基于程序性细胞死亡蛋白 1(PD-1)的治疗反应的关键特征,包括 CD163PD-L1 髓样细胞和 CD8FoxP3PD-1 T 细胞。这些特征被组合在一起以对 PD-1 阻断后的长期生存进行分层。该特征在来自不同机构的黑色素瘤患者的独立队列中得到了验证。