La Trobe
1196048_Goh,P_2022.pdf (5.23 MB)
Download file

PTPN2 elicits cell autonomous and non–cell autonomous effects on antitumor immunity in triple-negative breast cancer

Download (5.23 MB)
journal contribution
posted on 22.06.2022, 05:01 authored by PK Goh, F Wiede, MN Zeissig, KL Britt, S Liang, T Molloy, N Goode, R Xu, S Loi, M Muller, Patrick HumbertPatrick Humbert, C McLean, T Tiganis
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.

Funding

This work was supported by the Austrian Science Fund FWF (SFB F6101 and F6106 to M.M.), Worldwide Cancer Research (18-0045 to T.T. and C.M.), the U.S. Army Department of Defense (BC200609 to T.T.), and the NHMRC of Australia (APP1003037 to T.T.).

History

Publication Date

01/02/2022

Journal

Science Advances

Volume

8

Issue

8

Article Number

ARTN eabk3338

Pagination

22p.

Publisher

American Association for the Advancement of Science (AAAS)

ISSN

2375-2548

Rights Statement

© 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).