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.

中文翻译：

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T细胞中PTPN2磷酸酶的缺失可促进实体瘤中的抗肿瘤免疫力和CAR T细胞效力。

尽管过继性T细胞疗法已在血液系统恶性肿瘤中显示出显着的临床疗效，但其在对抗实体瘤方面的成功受到限制。在这里，我们报告说，T细胞中的PTPN2缺失增强了癌症的免疫监视和过继转移的肿瘤特异性T细胞的功效。T细胞特异的PTPN2缺乏可防止在肿瘤抑制因子p53杂合的老年小鼠中形成肿瘤。PTPN2缺陷型CD8 + T细胞的过继转移显着抑制了带有乳腺肿瘤的小鼠的肿瘤形成。此外，表达对癌蛋白HER-2有特异性的嵌合抗原受体（CAR）的T细胞中PTPN2缺失增加了Src家族激酶LCK的激活和细胞因子诱导的STAT-5信号传导，从而增强CAR T细胞活化和归巢于表达CXCL9 / 10的肿瘤，从而在体内根除HER-2 +乳腺肿瘤。我们的发现将PTPN2定义为增强T细胞介导的抗肿瘤免疫力和CAR T细胞治疗实体瘤的靶标。