Protein tyrosine phosphatase non-receptor type 2 controls colorectal cancer development.
- Katkeviciute E Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Hering L Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Montalban-Arques A Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Busenhart P Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Schwarzfischer M Department for Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Manzini R Department for Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Conde J Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Atrott K Department for Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Lang S Department for Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Rogler G Department for Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Naschberger E Division of Molecular and Experimental Surgery, University Medical Center of Erlangen, Erlangen, Germany.
- Schellerer VS Department of Surgery, University Medical Center of Erlangen, Erlangen, Germany.
- Stürzl M Division of Molecular and Experimental Surgery, University Medical Center of Erlangen, Erlangen, Germany.
- Rickenbacher A Department of Visceral and Transplant Surgery, University Hospital Zurich, Zurich, Switzerland.
- Turina M Department of Visceral and Transplant Surgery, University Hospital Zurich, Zurich, Switzerland.
- Weber A Department of Pathology, University Hospital Zurich, Zurich, Switzerland.
- Leibl S Department of Pathology, University Hospital Zurich, Zurich, Switzerland.
- Leventhal GE Department of Civil & Environmental Engineering, Massachusetts Institute of Technology, Cambridge, United States of America.
- Levesque M Department of Dermatology, University of Zürich, Zürich, Switzerland.
- Boyman O Department of Immunology, University Hospital Zurich, Zurich, Switzerland.
- Scharl M Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
- Spalinger MR Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.
- 2020-10-01
Published in:
- The Journal of clinical investigation. - 2020
English
Protein tyrosine phosphatase non-receptor type 2 (PTPN2) recently emerged as a promising cancer immunotherapy target. We set to investigate the functional role of PTPN2 in the pathogenesis of human colorectal carcinoma (CRC) as its role in immune-silent solid tumors is poorly understood. We demonstrate that in human CRC, increased PTPN2 expression and activity correlated with disease progression and decreased immune responses in tumor tissues. Particularly, stage II and III tumors displayed enhanced PTPN2 protein expression in tumor-infiltrating T-cells and increased PTPN2 levels negatively correlated with PD1, CTLA4, STAT1 and granzyme A. In vivo, T-cell and dendritic cell-specific PTPN2 deletion reduced tumor burden in several CRC models by promoting CD44+ effector/memory T-cells, as well as CD8+ T-cell infiltration and cytotoxicity into the tumor. In direct relevance to CRC treatment, T-cell-specific PTPN2 deletion potentiated anti-PD-1 efficacy and induced anti-tumor memory formation upon tumor re-challenge in vivo. Our data suggest a role for PTPN2 in suppressing anti-tumor immunity and promoting tumor development in CRC patients. Our in vivo results uncover PTPN2 as a key player in controlling immunogenicity of CRC, with the strong potential to be exploited to promote cancer immunotherapy.
- Language
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- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1172/JCI140281
- PMID 33001862
- Persistent URL
- https://sonar.ch/global/documents/230227
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