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

摘要

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 2 deletion in T cells enhances cancer immunosurveillance and the efficacy of adoptively transferred tumour‐specific T cells. T‐cell‐specific 2 deficiency prevented tumours forming in aged mice heterozygous for the tumour suppressor p53. Adoptive transfer of 2‐deficient 8 T cells markedly repressed tumour formation in mice bearing mammary tumours. Moreover, 2 deletion in T cells expressing a chimeric antigen receptor ( ) specific for the oncoprotein ‐2 increased the activation of the Src family kinase and cytokine‐induced ‐5 signalling, thereby enhancing both T‐cell activation and homing to 9/10‐expressing tumours to eradicate ‐2 mammary tumours . Our findings define 2 as a target for bolstering T‐cell‐mediated anti‐tumour immunity and T‐cell therapy against solid tumours.