Goh, Pei Kee (Monash University / Peter MacCallum Cancer Centre) Pei Kee Goh McLean, Catriona (Alfred Hospital) Catriona McLean Zeissig, Mara N. (Monash University / Peter MacCallum Cancer Centre) Mara N. Zeissig Wiede, Florian (Monash University / Peter MacCallum Cancer Centre) Florian Wiede Tiganis, Tony (Monash University / Peter MacCallum Cancer Centre) Tony Tiganis Humbert, Patrick O. (University of Melbourne / La Trobe University) Patrick O. Humbert Müller, Mathias (University of Veterinary Medicine Vienna) Mathias Müller Loi, Sherene (Peter MacCallum Cancer Centre / University of Melbourne) Sherene Loi Xu, Rachel (Monash University / Peter MacCallum Cancer Centre) Rachel Xu Goode, Nathan (La Trobe University) Nathan Goode Molloy, Tim (St. Vincent's Centre for Applied Medical Research) Tim Molloy Britt, Kara L. (Peter MacCallum Cancer Centre / The University of Melbourne) Kara L. Britt American Association for the Advancement of Science 2022 The tumor-suppressor PTPN2 is diminished in a subset of triple-negative breast cancers (TNBCs). Paradoxically, PTPN2-deficiency in tumors or T cells in mice can facilitate T cell recruitment and/or activation to promote antitumor immunity. Here, we explored the therapeutic potential of targeting PTPN2 in tumor cells and T cells. PTPN2-deficiency in TNBC associated with T cell infiltrates and PD-L1 expression, whereas low PTPN2 associated with improved survival. PTPN2 deletion in murine mammary epithelial cells TNBC models, did not promote tumorigenicity but increased STAT-1-dependent T cell recruitment and PD-L1 expression to repress tumor growth and enhance the efficacy of anti-PD-1. Furthermore, the combined deletion of PTPN2 in tumors and T cells facilitated T cell recruitment and activation and further repressed tumor growth or ablated tumors already predominated by exhausted T cells. Thus, PTPN2-targeting in tumors and/or T cells facilitates T cell recruitment and/or alleviates inhibitory constraints on T cells to combat TNBC. PDFDocument en 2023-07-03T12:15:41.656Z Protein-Tyrosine-Phosphatase; Tumor-Infiltrating Lymphocytes; Mediated Gene Deletion; Activation; Promotes; Obesity; Stat1; Expression; Generation; Relevance 5476370 b application/pdf CC BY-NC 4.0 International