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Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer

Publicado por
Wescott, EC, Sun, X, Gonzalez-Ericsson, P, Hanna, A, Taylor, BC, Sanchez, V, Bronzini, J, Opalenik, SR, Sanders, ME, Wulfkuhle, J, Gallagher, RI, Gomez, H, Isaacs, C, Bharti, V, Wilson, JT, Ballinger, TJ, Santa-Maria, CA, Shah, PD, Dees, EC, Lehmann, BD, Abramson, VG, Hirst, GL, Swigart, LB, van't, Veer, LJ, Esserman, LJ, Petricoin, EF, Pietenpol, JA, Balko, JM

Publicado 2024

Enlace

Combinations of immune checkpoint inhibitors (ICI, including anti-PD-1/PD-L1) and chemotherapy have been FDA approved for metastatic and early-stage triple-negative breast cancer (TNBC), but most patients do not benefit. B7-H4 is a B7 family ligand with proposed immunosuppressive functions being explored as a cancer immunotherapy target and may be associated with anti-PD-L1 resistance. However, little is known about its regulation and effect on immune cell function in breast cancers. We assessed murine and human breast cancer cells to identify regulation mechanisms of B7-H4 in vitro. We used an immunocompetent anti-PD-L1–sensitive orthotopic mammary cancer model and induced ectopic expression of B7-H4. We assessed therapy response and transcriptional changes at baseline and under treatment with anti-PD-L1. We observed B7-H4 was highly associated with epithelial cell status and transcri...