Unmasking the Many Faces of Tumor-Associated Neutrophils and Macrophages: Considerations for Targeting Innate Immune Cells in Cancer

Immunotherapy has emerged at the forefront of cancer therapy; however, patient survival remains low for many cancer types. In consideration of this, non-T cell immune populations, such as innate immune cells, have been identified as potential immunotherapeutic targets. In noncancerous settings, neutrophils are first responders to injury and infection, and work in a partnership with macrophages to regulate inflammation. However, the diversity of tumor-associated neutrophils (TANs) remains elusive. Furthermore, it is likely that TANs and tumor-associated macrophages (TAMs) act in tandem within tumors and contribute both contrasting and synergistic roles in tumor progression. In this Opinion, we discuss the complexity of TAN and TAM functions, the interplay between TANs and TAMs, and major considerations required for implementing TAN/TAM-based therapies.