Immunosuppressive myeloid cells induce mesenchymal-like breast cancer stem cells by a mechanism involving membrane-bound TGF-β1

Suppressive myeloid cells play a central role in cancer escape from anti-tumor immunity. Beyond their immunosuppressive function, these cells are capable of exerting multiple other pro-tumoral activities, including the promotion of cancer cell survival, invasion and metastasis. The ability of some myeloid subsets to induce cancer stemness has recently emerged. Here we demonstrated that human immunosuppressive myeloid cells, generated in vitro or isolated from breast cancer patients, promoted the acquisition of mesenchymal-like breast cancer stemness properties. This cancer-stemness-inducing function was restricted to a myeloid subset expressing the glycoprotein CD52. Single cell transcriptomic- and surface proteome-based interactome analysis pointed towards membrane-bound TGF-β1 as a potential factor involved in cancer stemness induction. Functional inhibition of the TGF-β1 pathway blocked the emergence of cancer stem cells induced by suppressive myeloid cells. These results therefore identified the underlying mechanisms of a new tumor-promoting function of immunosuppressive myeloid cells, which may potentially be targeted.