An Immune Atlas of Clear Cell Renal Cell Carcinoma

Stéphane Chevrier; Jacob Harrison Levine; Vito Riccardo Tomaso Zanotelli; Karina Silina; Daniel Schulz; Marina Bacac; Carola Hermine Ries; Laurie Ailles; Michael Alexander Spencer Jewett; Holger Moch; Maries van den Broek; Christian Beisel; Michael Beda Stadler; Craig Gedye; Bernhard Reis; Dana Pe'er; Bernd Bodenmiller

doi:10.1016/j.cell.2017.04.016

An Immune Atlas of Clear Cell Renal Cell Carcinoma

Cell. 2017 May 4;169(4):736-749.e18. doi: 10.1016/j.cell.2017.04.016.

Authors

Stéphane Chevrier¹, Jacob Harrison Levine², Vito Riccardo Tomaso Zanotelli³, Karina Silina⁴, Daniel Schulz¹, Marina Bacac⁵, Carola Hermine Ries⁶, Laurie Ailles⁷, Michael Alexander Spencer Jewett⁸, Holger Moch⁹, Maries van den Broek⁴, Christian Beisel¹⁰, Michael Beda Stadler¹¹, Craig Gedye¹², Bernhard Reis¹³, Dana Pe'er², Bernd Bodenmiller¹⁴

Affiliations

¹ Institute of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
² Computational and Systems Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
³ Institute of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Systems Biology PhD Program, Life Science Zürich Graduate School, ETH Zürich and University of Zürich, 8057 Zürich, Switzerland.
⁴ Institute of Experimental Immunology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
⁵ Roche Pharma Research and Early Development, Roche Innovation Center Zürich, Wagistrasse 18, 8952 Schlieren, Switzerland.
⁶ Roche Pharma Research and Early Development, Roche Innovation Center Munich, Nonnenwald 2, 82377 Penzberg, Germany.
⁷ Department of Medical Biophysics, University of Toronto, Toronto ON M5G 1L7, Canada; Princess Margaret Cancer Center, University Health Network, Toronto ON M5G 1L7, Canada.
⁸ Princess Margaret Cancer Center, University Health Network, Toronto ON M5G 1L7, Canada.
⁹ Institute for Surgical Pathology, University Hospital Zürich, Schmelzbergstrasse 12, 8091 Zürich, Switzerland.
¹⁰ Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.
¹¹ Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; Swiss Institute of Bioinformatics, Mattenstrasse 26, 4058 Basel, Switzerland.
¹² School of Biomedical Sciences and Pharmacy, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW 2035, Australia.
¹³ Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Grenzacherstrasse 124, 4070 Basel, Switzerland.
¹⁴ Institute of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. Electronic address: bernd.bodenmiller@imls.uzh.ch.

Abstract

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.

Keywords: T cell; clear cell renal cell carcinoma; immune cell atlas; immunosuppression; macrophage; mass cytometry; single-cell analysis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Renal Cell / immunology*
Carcinoma, Renal Cell / pathology*
Humans
Image Cytometry
Immune Tolerance
Kidney / cytology
Kidney Neoplasms / immunology*
Kidney Neoplasms / pathology*
Macrophages / immunology
Macrophages / pathology
Single-Cell Analysis
T-Lymphocytes / immunology
T-Lymphocytes / pathology
Tumor Microenvironment*

Abstract

Publication types

MeSH terms

Grants and funding