PTPN2 phosphatase deletion in T cells promotes anti-tumour immunity and CAR T-cell efficacy in solid tumours.
EMBO J
; 39(2): e103637, 2020 01 15.
Article
em En
| MEDLINE
| ID: mdl-31803974
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 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Receptores de Antígenos de Linfócitos T
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Imunoterapia Adotiva
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Receptor ErbB-2
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Linfócitos T CD8-Positivos
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Proteína Tirosina Fosfatase não Receptora Tipo 2
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Neoplasias
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Austrália