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PTPN 2 phosphatase deletion in T cells promotes anti‐tumour immunity and CAR T‐cell efficacy in solid tumours
Author(s) -
Wiede Florian,
Lu KunHui,
Du Xin,
Liang Shuwei,
Hochheiser Katharina,
Dodd Garron T,
Goh Pei K,
Kearney Conor,
Meyran Deborah,
Beavis Paul A,
Henderson Melissa A,
Park Simone L,
Waithman Jason,
Zhang Sheng,
Zhang ZhongYin,
Oliaro Jane,
Gebhardt Thomas,
Darcy Phillip K,
Tiganis Tony
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019103637
Subject(s) - biology , adoptive cell transfer , immunosurveillance , cancer research , chimeric antigen receptor , cd8 , t cell , immunology , homing (biology) , cytotoxic t cell , antigen , immune system , in vitro , ecology , biochemistry
Abstract 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 PTPN 2 deletion in T cells enhances cancer immunosurveillance and the efficacy of adoptively transferred tumour‐specific T cells. T‐cell‐specific PTPN 2 deficiency prevented tumours forming in aged mice heterozygous for the tumour suppressor p53. Adoptive transfer of PTPN 2‐deficient CD 8 + T cells markedly repressed tumour formation in mice bearing mammary tumours. Moreover, PTPN 2 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 CXCL 9/10‐expressing tumours to eradicate HER ‐2 + mammary tumours in vivo . Our findings define PTPN 2 as a target for bolstering T‐cell‐mediated anti‐tumour immunity and CAR T‐cell therapy against solid tumours.