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Fig. 7 | Journal for ImmunoTherapy of Cancer

Fig. 7

From: Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments

Fig. 7

Ovarian cancer stem cells and macrophages reciprocally interact through the Wnt pathway to promote a pro-tumoral microenvironment. Our data suggests that in hetero-spheroids, CSCs drive a CD206+ expressing macrophage phenotype, suggestive of pro-tumoral M2 activation through secretion of the immuno-suppressive cytokine IL-10, and through WNT ligands. We also observe that macrophage-derived WNT ligands, specifically WNT5B, and to some extent the pro-tumoral cytokine IL-6, drive an enrichment in ALDH+ cells within hetero-spheroids. Knockdown of macrophage WNT5B expression, or inhibiting downstream activation of IL-6 using Ruxolitinib or sc144, result in a significant loss of ALDH+ populations within hetero-spheroids. Importantly, we find that the Wnt pathway is involved bi-directionally in CSC-macrophage interactions, and can potentially be targeted to reduce stemness, chemoresistance, invasiveness and immunosuppression in ovarian cancer

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