SOS1i+MEKi co-opt an immunosuppressive microenvironment by iCAF-M2 macrophage interactions and dendritic cell activation defects. A, UMAP visualization of subsets of CAFs, myeloid cells and T/NK cells. B, Bar graph showing cell proportion/composition of indicated cell subset type in the (mean ± 95% confidence interval). C, Heat map of frequency correlation (Pearson correlation coefficient) between every pair of nonmalignant cells in the TME. D, Interaction number between nonmalignant cell types. E, Interaction strength centered around iCAF before (top) and after SOS1i+MEKi treatment (bottom). F, Pathway enrichment analysis of upregulated and downregulated genes in macrophages in response to SOS1i+MEKi treatment. G, Dot plot showing gene expression of M2 macrophage polarization genes
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Norgard et al. (2024) studied this question.
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