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EMBO J. 2020 Jan 15;39(2):e103637. doi: 10.15252/embj.2019103637. Epub 2019 Dec 5.

PTPN2 phosphatase deletion in T cells promotes anti-tumour immunity and CAR T-cell efficacy in solid tumours.

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Monash Biomedicine Discovery Institute, Monash University, Clayton, Vic., Australia.
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic., Australia.
Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Vic., Australia.
Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Vic., Australia.
Peter Doherty Institute for Infection and Immunity, Melbourne, Vic., Australia.
Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Department of Medicinal Chemistry and Molecular Pharmacology, Institute for Drug Discovery, Purdue University, West Lafayette, IN, USA.


Although adoptive T-cell therapy has shown remarkable clinical efficacy in haematological malignancies, its success in combating solid tumours has been limited. Here, we report that PTPN2 deletion in T cells enhances cancer immunosurveillance and the efficacy of adoptively transferred tumour-specific T cells. T-cell-specific PTPN2 deficiency prevented tumours forming in aged mice heterozygous for the tumour suppressor p53. Adoptive transfer of PTPN2-deficient CD8+ T cells markedly repressed tumour formation in mice bearing mammary tumours. Moreover, PTPN2 deletion in T cells expressing a chimeric antigen receptor (CAR) specific for the oncoprotein HER-2 increased the activation of the Src family kinase LCK and cytokine-induced STAT-5 signalling, thereby enhancing both CAR T-cell activation and homing to CXCL9/10-expressing tumours to eradicate HER-2+ mammary tumours in vivo. Our findings define PTPN2 as a target for bolstering T-cell-mediated anti-tumour immunity and CAR T-cell therapy against solid tumours.


CAR T cells; STAT-5 signalling; TCR signalling; adoptive T-cell therapy; protein tyrosine phosphatase N2

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