Functional states of myeloid cells in cancer

Myeloid cells, comprised of macrophages, dendritic cells, monocytes, and granulocytes, represent a major component of the tumor microenvironment (TME) and are critically involved in regulation of tumor progression and metastasis. In recent years, single-cell omics technologies have identified multiple phenotypically distinct subpopulations. In this review, we discuss recent data and concepts suggesting that the biology of myeloid cells is largely defined by a very limited number of functional states that transcend the narrowly defined cell populations. These functional states are primarily centered around classical and pathological states of activation, with the latter state commonly defined as myeloid-derived suppressor cells. We discuss the concept that lipid peroxidation of myeloid cells represents a major mechanism that governs their pathological state of activation in the TME. Lipid peroxidation is associated with ferroptosis mediating suppressive activity of these cells and thus could be considered an attractive target for therapeutic intervention. Van Vlerken-Ysla et al. discuss that functional states of myeloid cells transcend single-cell omics-based cell clusters and outline factors involved in diversification of these cells in the bone marrow, periphery, and tumor microenvironment. They propose that lipid peroxidation represents a major mechanism governing their pathological state of activation, potentially providing a therapeutic vulnerability.