PTPN2 elicits cell autonomous and non-cell autonomous effects on antitumor immunity in triple-negative breast cancer
- Author(s)
- Goh, PK; Wiede, F; Zeissig, MN; Britt, KL; Liang, S; Molloy, T; Goode, N; Xu, R; Loi, S; Muller, M; Humbert, PO; McLean, C; Tiganis, T;
- Details
- Publication Year 2022-02-25,Volume 8,Issue #8,Page eabk3338
- Journal Title
- Science Advances
- Publication Type
- Research article
- Abstract
- 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.
- Keywords
- Animals; B7-H1 Antigen/metabolism; Cell Line, Tumor; Humans; Mice; Protein Tyrosine Phosphatase, Non-Receptor Type 2/genetics; *Triple Negative Breast Neoplasms/drug therapy
- Department(s)
- Laboratory Research; Medical Oncology
- PubMed ID
- 35196085
- Publisher's Version
- https://doi.org/10.1126/sciadv.abk3338
- Open Access at Publisher's Site
https://doi.org/10.1126/sciadv.abk3338- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-10-31 04:55:11
Last Modified: 2024-10-31 04:56:11