Whole-genome doubling promotes immune evasion in TNBC by epigenetically silencing antigen presentation pathways through PRC2 activity. (SABCS 2025) - Oct 31, 2025 - Abstract #PS2-11-27; Pres time: Dec 10, 2025; 05:00 PM - 06:30 PM; Location: Exhibit Hall; "Through single-cell profiling, we found that WGD+ cancer cells exhibit impaired antigen presentation, driven in part by a reduced response to IFN-γ and epigenetic silencing of MHC class I transcriptional regulators via the PRC2 complex.Treatment with a PRC2 inhibitor preferentially inhibited WGD+ tumor growth, restored antigen presentation, and enhanced CD8⁺ T cell infiltration. These findings suggest that combined inhibition of PRC2 and PD-1 represents a promising therapeutic approach for WGD+ breast cancers."
Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Triple Negative Breast Cancer • CD8 • HER-2 • IFNG
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P. Foidart1; Z. Li1; X. Can1; M. Seehawer1; E. Rojas-Jimenez1; P. Baldominos2; J. Nishida1; T. Bui1; B. Diciaccio1; S. Parvin1; M. Goyette1; P. Yan1; X. Qiu3; R. Li3; Y. Jiang3; Y. Xie3; X. Huang1; L. E. Stevens1; P. Cejas3; L. Mangiante4; C. I. Sotomayor Vivas4; K. Houlahan4; T. Scales5; I. S. Harris5; C. Curtis4; A. G. Letai1; H. W. Long3; J. Agudo2; K. Polyak1
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