A Single-Cell Tumor Immune Atlas for Precision Oncology

The tumor immune microenvironment is a main contributor to cancer progression and a promising therapeutic target for oncology. However, immune microenvironments vary profoundly between patients and biomarkers for prognosis and treatment response lack precision. A comprehensive compendium of tumor immune cells is required to pinpoint predictive cellular states and their spatial localization. We generated a single-cell resolved tumor immune cell atlas, jointly analyzing >500,000 cells from 217 patients and 13 cancer types, providing the basis for a patient stratification based on immune cell compositions. Projecting immune cells from external tumors onto the atlas facilitated an automated cell annotation system for a harmonized interpretation. To enable in situ mapping of immune populations for digital pathology, we developed SPOTlight, a computational tool that identified striking spatial immune cell patterns in tumor sections. We expect the atlas, together with our versatile toolbox for precision oncology, to advance currently applied stratification strategies for prognosis and immuno-therapy response. Single-cell RNA sequencing was performed on two human uveal melanoma cancers, one human ovarian cancer, one human uveal melanoma liver metastasis, one human non-small cell lung cancer brain metastasis (including TCR), two human head and neck cancers and two mice colorectal cancers (one full and one only T cells and TCR)