Developmental pathways of myeloid-derived suppressor cells in neoplasia

Immunotherapy has become a major weapon against the war on cancer. This has culminated from decades of seminal work that led to the discovery of innovative approaches to drive adaptive immunity. Notably, was the discovery of immune checkpoint inhibitory receptors on T cells, and the subsequent development of monoclonal antibodies that target those receptors, known as immune checkpoint inhibitors (ICIs). Blocking those receptors using ICIs leads to sustained effector function, which has translated to enhanced antitumor responses across multiple human cancer types. However, these treatments are effective in subsets of patients, implicating significant barriers limiting therapeutic potential. While numerous mechanisms may hinder immunotherapy potency, one prominent mechanism is the production of myeloid-derived suppressor cells (MDSCs). MDSCs comprise monocytic and granulocytic cell types and mediate pro-tumorigenic and immune suppressive activities. Here, we summarize several pathways by which MDSCs arise in cancer, providing a conceptual framework for identifying unique combination therapeutic interventions.