PTPN2 elicits cell autonomous and non–cell autonomous effects on antitumor immunity in triple-negative breast cancer
Science advances, 2022•science.org
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 …
(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 …
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.
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