TY - JOUR T1 - PTPN2 deletion in T cells promotes anti-tumour immunity and CAR T cell efficacy in solid tumours JF - bioRxiv DO - 10.1101/757419 SP - 757419 AU - Florian Wiede AU - Kun-Hui Lu AU - Xin Du AU - Shuwei Liang AU - Katharina Hochheiser AU - Garron T. Dodd AU - Pei Goh AU - Conor Kearney AU - Deborah Meyran AU - Paul A. Beavis AU - Melissa A. Henderson AU - Simone L. Park AU - Jason Waithman AU - Sheng Zhang AU - Zhong-Yin Zhang AU - Jane Oliaro AU - Thomas Gebhardt AU - Phillip K. Darcy AU - Tony Tiganis Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/09/05/757419.abstract N2 - Although adoptive T cell therapy has shown remarkable clinical efficacy in hematological 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. ER -