FIGURE 2 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Year: 2024
Type: other
Abstract: B7-H4 (VTCN1) is highly correlated with epithelial gene markers in mouse and human cells unlike other checkpoint ligands. A, In human breast cancer cell lines (CCLE), B7-H4 is the only checkpoint ligand positively correlated with epithelial markers and negatively correlated with mesenchymal markers. Data shown are Spearman correlations between genes. Significant correlations (P < 0.05) are indicated by asterisk. B, Genes downregulated during EMT are positively correlated with VTCN1 in human cell lines (CCLE). C, Murine cancer cell lines express B7-H4. D, B7-H4 is only expressed on epithelial EpCAM+ cells in murine and human cells. E, The MMTV-neu cell line with highest B7-H4 levels is comprised of phenotypically epithelial-like (abbreviated E) and mesenchymal-like (M) cells. F, In MMTV-neu cells, the CD44+ M cells do not express B7-H4 but all the EpCAM+ E cells do. G, MMTV-neu E and M cells express hallmark markers. H, Single-cell RNA sequencing of the heterogenous MMTV-neu cells confirms Vtcn1 is solely expressed in the epithelial cell population. I, A cohort of human tumors including both TNBC and ER+HER2− were stained for B7-H4, EpCAM, and CD44 by mIF. Data shown are log2 of % B7-H4+ tumor cells and include 132 samples with >1% B7-H4 expression (paired t test of transformed data).
Authors: Elizabeth C. Wescott, Xiaopeng Sun, Paula Gonzalez-Ericsson, Ann Hanna, Brandie C. Taylor, Violeta Sanchez, Juliana Bronzini, Susan R. Opalenik, Melinda E. Sanders, Julia Wulfkuhle, Rosa I. Gallagher, Henry Gomez, Claudine Isaacs, Vijaya Bharti, John T. Wilson, Tarah J. Ballinger, Cesar A. Santa-Maria, Payal D. Shah, Elizabeth C. Dees, Brian D. Lehmann, Vandana G. Abramson, Gillian L. Hirst, Lamorna Brown Swigart, Laura J. van ˈt Veer, Laura J. Esserman, Emanuel F. Petricoin, Jennifer A. Pietenpol, Justin M. Balko
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4395082265