Chevrier Stéphane, Levine Jacob Harrison, Zanotelli Vito Riccardo Tomaso, Silina Karina, Schulz Daniel, Bacac Marina, Ries Carola Hermine, Ailles Laurie, Jewett Michael Alexander Spencer, Moch Holger, van den Broek Maries, Beisel Christian, Stadler Michael Beda, Gedye Craig, Reis Bernhard, Pe'er Dana, Bodenmiller Bernd
Institute of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Computational and Systems Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
Cell. 2017 May 4;169(4):736-749.e18. doi: 10.1016/j.cell.2017.04.016.
Immune cells in the tumor microenvironment modulate cancer progression and are attractive therapeutic targets. Macrophages and T cells are key components of the microenvironment, yet their phenotypes and relationships in this ecosystem and to clinical outcomes are ill defined. We used mass cytometry with extensive antibody panels to perform in-depth immune profiling of samples from 73 clear cell renal cell carcinoma (ccRCC) patients and five healthy controls. In 3.5 million measured cells, we identified 17 tumor-associated macrophage phenotypes, 22 T cell phenotypes, and a distinct immune composition correlated with progression-free survival, thereby presenting an in-depth human atlas of the immune tumor microenvironment in this disease. This study revealed potential biomarkers and targets for immunotherapy development and validated tools that can be used for immune profiling of other tumor types.
肿瘤微环境中的免疫细胞调节癌症进展,是有吸引力的治疗靶点。巨噬细胞和T细胞是微环境的关键组成部分,然而它们在这个生态系统中的表型及其与临床结果的关系尚不明确。我们使用带有广泛抗体组的质谱流式细胞术对73例透明细胞肾细胞癌(ccRCC)患者和5名健康对照的样本进行了深入的免疫分析。在350万个测量细胞中,我们鉴定出17种肿瘤相关巨噬细胞表型、22种T细胞表型,以及一种与无进展生存期相关的独特免疫组成,从而呈现了这种疾病免疫肿瘤微环境的深入人类图谱。这项研究揭示了免疫治疗开发的潜在生物标志物和靶点,并验证了可用于其他肿瘤类型免疫分析的工具。