PTPN2 phosphatase deletion in T cells promotes anti-tumour immunity and CAR T-cell efficacy in solid tumours
Florian Wiede, Kun-Hui Lu, Xin Du, Shuwei Liang, Katharina Hochheiser, Garron T Dodd, Pei K Goh, Conor Kearney, Deborah Meyran, Paul A Beavis, Melissa A Henderson, Simone L Park, Jason Waithman, Sheng Zhang, Zhong-Yin Zhang, Jane Oliaro, Thomas Gebhardt, Phillip K Darcy, Tony Tiganis
EMBO JOURNAL | WILEY | Published : 2020
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 fa..View full abstract
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This work was supported by the National Health and Medical Research Council (NHMRC) of Australia (to T.T., P.K.D.), Sylvia & Charles Viertel Charitable Foundation (T.G.), Cancer Council Victoria (F.W.) and the NIH (Z.Y.).