https://phaidra.vetmeduni.ac.at/o:1787 PTPN2 elicits cell autonomous and non-cell autonomous effects on antitumor immunity in triple-negative breast cancer Goh, Pei Kee Pei Kee Goh 0000-0001-9404-6058 Monash University / Peter MacCallum Cancer Centre McLean, Catriona Catriona McLean 0000-0002-0302-5727 Alfred Hospital Tiganis, Tony Tony Tiganis 0000-0002-8065-9942 Monash University / Peter MacCallum Cancer Centre Humbert, Patrick O. Patrick O. Humbert 0000-0002-1366-6691 University of Melbourne / La Trobe University Müller, Mathias Mathias Müller University of Veterinary Medicine Vienna Loi, Sherene Sherene Loi 0000-0001-6137-9171 Peter MacCallum Cancer Centre / University of Melbourne Xu, Rachel Rachel Xu Monash University / Peter MacCallum Cancer Centre Goode, Nathan Nathan Goode 0000-0002-3413-407X La Trobe University Molloy, Tim Tim Molloy St. Vincent's Centre for Applied Medical Research Britt, Kara L. Kara L. Britt 0000-0002-0359-505X Peter MacCallum Cancer Centre / The University of Melbourne Zeissig, Mara N. Mara N. Zeissig Monash University / Peter MacCallum Cancer Centre Wiede, Florian Florian Wiede 0000-0001-5145-7180 Monash University / Peter MacCallum Cancer Centre American Association for the Advancement of Science text eng 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. Protein-Tyrosine-Phosphatase; Tumor-Infiltrating Lymphocytes; Mediated Gene Deletion; Activation; Promotes; Obesity; Stat1; Expression; Generation; Relevance http://creativecommons.org/licenses/by-nc/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:1787/download 10.1126/sciadv.abk3338 https://phaidra.vetmeduni.ac.at/o:605 application/pdf Science Advances 8(8) (2022) Science Advances 8 8 5.22 MB 2022