Nature Communications (Feb 2023)
Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy
- Marcel P. Trefny,
- Nicole Kirchhammer,
- Priska Auf der Maur,
- Marina Natoli,
- Dominic Schmid,
- Markus Germann,
- Laura Fernandez Rodriguez,
- Petra Herzig,
- Jonas Lötscher,
- Maryam Akrami,
- Jane C. Stinchcombe,
- Michal A. Stanczak,
- Andreas Zingg,
- Melanie Buchi,
- Julien Roux,
- Romina Marone,
- Leyla Don,
- Didier Lardinois,
- Mark Wiese,
- Lukas T. Jeker,
- Mohamed Bentires-Alj,
- Jérémie Rossy,
- Daniela S. Thommen,
- Gillian M. Griffiths,
- Heinz Läubli,
- Christoph Hess,
- Alfred Zippelius
Affiliations
- Marcel P. Trefny
- Laboratory of Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Nicole Kirchhammer
- Laboratory of Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Priska Auf der Maur
- Laboratory of Tumor Heterogeneity, Metastasis and Resistance, Department of Biomedicine, University of Basel and University Hospital of Basel
- Marina Natoli
- Laboratory of Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Dominic Schmid
- Laboratory of Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Markus Germann
- Laboratory of Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Laura Fernandez Rodriguez
- Laboratory of Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Petra Herzig
- Laboratory of Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Jonas Lötscher
- Laboratory of Immunobiology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Maryam Akrami
- Laboratory of Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Jane C. Stinchcombe
- Cambridge Institute for Medical Research, Biomedical Campus
- Michal A. Stanczak
- Laboratory of Cancer Immunotherapy, Department of Biomedicine, University of Basel and University Hospital of Basel
- Andreas Zingg
- Laboratory of Cancer Immunotherapy, Department of Biomedicine, University of Basel and University Hospital of Basel
- Melanie Buchi
- Laboratory of Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Julien Roux
- Bioinformatics Core Facility, Department of Biomedicine, University of Basel and University Hospital of Basel
- Romina Marone
- Laboratory of Molecular Immune Regulation, Department of Biomedicine, University of Basel and University Hospital of Basel
- Leyla Don
- Laboratory of Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Didier Lardinois
- Department of Surgery, University Hospital Basel
- Mark Wiese
- Department of Surgery, University Hospital Basel
- Lukas T. Jeker
- Laboratory of Molecular Immune Regulation, Department of Biomedicine, University of Basel and University Hospital of Basel
- Mohamed Bentires-Alj
- Laboratory of Tumor Heterogeneity, Metastasis and Resistance, Department of Biomedicine, University of Basel and University Hospital of Basel
- Jérémie Rossy
- Biotechnology Institute Thurgau, University of Konstanz
- Daniela S. Thommen
- Laboratory of Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Gillian M. Griffiths
- Cambridge Institute for Medical Research, Biomedical Campus
- Heinz Läubli
- Laboratory of Cancer Immunotherapy, Department of Biomedicine, University of Basel and University Hospital of Basel
- Christoph Hess
- Laboratory of Immunobiology, Department of Biomedicine, University of Basel and University Hospital of Basel
- Alfred Zippelius
- Laboratory of Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel
- DOI
- https://doi.org/10.1038/s41467-022-35583-w
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 21
Abstract
The efficacy of T-cell-based cancer immunotherapies can be compromised by T cell exhaustion. Here the authors develop a human ex vivo exhaustion model and, based on a CRISPR-Cas9 screen, identify SNX9 as a regulator of T cell exhaustion, showing that SNX9 knockout is associated with improved T cell function and anti-tumor activity in preclinical cancer models.
