Protein tyrosine phosphatase nonreceptor type 2 controls colorectal cancer development

Katkeviciute E, Hering L, Montalban-Arques A, Busenhart P, Schwarzfischer M, Manzini R, Conde J, Atrott K, Lang S, Rogler G, Naschberger E, Schellerer V, Stürzl M, Rickenbacher A, Turina M, Weber A, Leibl S, Leventhal GE, Levesque M, Boyman O, Scharl M, Spalinger MR (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Journal of Clinical Investigation American Society for Clinical Investigation

Book Volume: 131

Article Number: e140281

Journal Issue: 1

DOI: 10.1172/JCI140281

Abstract

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) recently emerged as a promising cancer immunotherapy target. We set out 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. In particular, stage II and III tumors displayed enhanced PTPN2 protein expression in tumor-infiltrating T cells, and increased PTPN2 levels negatively correlated with expression of PD-1, CTLA4, STAT1, and granzyme A. In vivo, T cell- and DC-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 in the tumor. In direct relevance to CRC treatment, T cell-specific PTPN2 deletion potentiated anti-PD-1 efficacy and induced antitumor memory formation upon tumor rechallenge in vivo. Our data suggest a role for PTPN2 in suppressing antitumor immunity and promoting tumor development in patients with CRC. Our in vivo results identify PTPN2 as a key player in controlling the immunogenicity of CRC, with the strong potential to be exploited for cancer immunotherapy.

Authors with CRIS profile

Elisabeth Naschberger Medizinische Fakultät Vera Schellerer Department of Surgery Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie

Involved external institutions

Universitätsspital Zürich (USZ) CH Switzerland (CH) Massachusetts Institute of Technology (MIT) US United States (USA) (US)

How to cite

APA:

Katkeviciute, E., Hering, L., Montalban-Arques, A., Busenhart, P., Schwarzfischer, M., Manzini, R.,... Spalinger, M.R. (2021). Protein tyrosine phosphatase nonreceptor type 2 controls colorectal cancer development. Journal of Clinical Investigation, 131(1). https://doi.org/10.1172/JCI140281

MLA:

Katkeviciute, Egle, et al. "Protein tyrosine phosphatase nonreceptor type 2 controls colorectal cancer development." Journal of Clinical Investigation 131.1 (2021).

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