o:1787 PTPN2 elicits cell autonomous and non-cell autonomous effects on antitumor immunity in triple-negative breast cancer en 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 1552099 10.1126/sciadv.abk3338 2023-07-03T12:15:41.656Z 44 yes 46 Pei Kee Goh Monash University / Peter MacCallum Cancer Centre 0000-0001-9404-6058 Catriona McLean Alfred Hospital person 0000-0002-0302-5727 Tony Tiganis Monash University / Peter MacCallum Cancer Centre person 0000-0002-8065-9942 Patrick O. Humbert University of Melbourne / La Trobe University person 0000-0002-1366-6691 Mathias Müller University of Veterinary Medicine Vienna person Sherene Loi Peter MacCallum Cancer Centre / University of Melbourne person 0000-0001-6137-9171 Rachel Xu Monash University / Peter MacCallum Cancer Centre person Nathan Goode La Trobe University person 0000-0002-3413-407X Tim Molloy St. Vincent's Centre for Applied Medical Research person Kara L. Britt Peter MacCallum Cancer Centre / The University of Melbourne person 0000-0002-0359-505X Mara N. Zeissig Monash University / Peter MacCallum Cancer Centre person Florian Wiede Monash University / Peter MacCallum Cancer Centre person 0000-0001-5145-7180 application/pdf 5476370 https://phaidra.vetmeduni.ac.at/o:1787 no yes 17 70 1552253 Science Advances 23 8 8 American Association for the Advancement of Science 2022