An Immune Atlas of Clear Cell Renal Cell Carcinoma

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. [Display omitted] •Mass cytometry reveals the immune cell diversity of the ccRCC tumor ecosystem•PD-1+ cells display heterogeneous combinations of inhibitory receptors•CD38+CD204+CD206− tumor-associated macrophages correlate with immunosuppression•A specific immune signature is linked to shorter progression-free survival Applying mass cytometry for high-dimensional single-cell analysis depicts an in-depth atlas of the immune microenvironment in clear cell renal cell carcinoma patients, thereby linking immune compositions with clinical features.