Myeloid cells in the era of cancer immunotherapy: Top 3 unanswered questions

Myeloid cells are increasingly being recognized as central players orchestrating or suppressing antitumor immune responses. With the advent of high-resolution analytical methods such as single-cell technologies, we now appreciate the heterogeneity and complexity of the myeloid compartment in the context of cancer. Because of their highly plastic nature, targeting myeloid cells has shown promising results either as a monotherapy or in combination with immunotherapy in preclinical models and cancer patients. However, the complexity of myeloid cell cellular crosstalk and molecular networks contributes to our poor understanding of the different myeloid cell subsets in tumorigenesis, which makes targeting myeloid cells challenging. Here, we summarize varied myeloid cell subsets and their contribution to tumor progression with a main focus on mononuclear phagocytes. The top three unanswered questions challenging the field of myeloid cells and cancer in the era of cancer immunotherapy are addressed. Through these questions, we discuss how myeloid cell origin and identity influence their function and disease outcomes. Different therapeutic strategies used to target myeloid cells in cancer are also addressed. Finally, the durability of myeloid cell targeting is interrogated by examining the complexity of resultant compensatory cellular and molecular mechanisms.