The Emerging Understanding of Myeloid Cells as Partners and Targets in Tumor Rejection

Myeloid cells are the most prominent among cells capable of presenting tumor-derived antigens to T cells and thereby maintaining the latter in an activated state. Myeloid populations of the tumor microenvironment prominently include monocytes and neutrophils (sometimes loosely grouped as myeloid-derived suppressor cells), macrophages, and dendritic cells. Although intratumoral myeloid populations, as a whole, have long been considered nonstimulatory or suppressive, it has only recently been appreciated that not all tumor-infiltrating myeloid cells are made equal. Because of advances in high-dimensional flow cytometry as well as more robust transcriptional profiling, we now also understand that the subsets of the tumor-myeloid compartment are far more diverse and notably even contain a rare population of stimulatory dendritic cells. As all of these myeloid populations represent major T-cell-interacting partners for incoming tumor-reactive cytotoxic T lymphocytes, understanding the distinctions in their lineage and function reveals and guides numerous therapeutic avenues targeting these antigen-presenting cells. In this Cancer Immunology at the Crossroads overview, we review the recent progress in this rapidly evolving field and advance the hypothesis that the antigen-presenting compartment within tumor microenvironments may contain significant numbers of potent allies to be leveraged for immune-based tumor clearance.