Fig. 2

Juxtacrine mechanisms of interaction between cancer stem cells (CSCs) and tumor-associated macrophages (TAM). CSCs upregulate the enzyme hyaluronan synthase 2 (HAS2), which induces the formation of a layer of pericellular hyaluronan (HA) that facilitates their attachment to TAMs, via the CD44 receptor. Upon this interaction, TAMs produce the growth factor PDGF-BB, which enhances CSC self-renewal; moreover, it activates signaling pathways important for CSC maintenance (e.g.PI3K–4EBP1–SOX2). CSCs express CD90 and the receptor EphA4, which bind to CD11b and Ephrin, respectively. These interactions activate the Src/NFkB pathway, and together with the LSECtin and BTN3A3 they support and drive cancer stemness. Finally, CSCs downregulate MHC molecules and CD80, while upregulating PD-1L, CD47, B7-H3 to escape from the immune system recognition. This figure was made with Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0. Unported License (https://smart.servier.com)