A drug development perspective on targeting tumor-associated myeloid cells

Despite decades of research, Cancer remains a devastating disease and new treatment options are needed. Today Cancer is acknowledged as a multifactorial disease not only comprising of aberrant tumor cells but also the associated stroma including tumor vasculature, fibrotic plaques, and immune cells that interact in a complex heterotypic interplay. Myeloid cells represent one of the most abundant immune cell population within the tumor stroma and are equipped with a broad functional repertoire that promotes tumor growth by suppressing cytotoxic T cell activity, stimulating neoangiogenesis and tissue remodeling. Therefore, myeloid cells have become an attractive target for pharmacological intervention. In this review, we summarize the pharmacological approaches to therapeutically target tumor-associated myeloid cells with a focus on advanced programs that are clinically evaluated. In addition, for each therapeutic strategy, the preclinical rationale as well as advantages and challenges from a drug development perspective are discussed.

CCL2; CD40; CD47; CSF-1R; depletion; reprogramming; trabectedin; tumor microenvironment; tumor-associated macrophages; tumor-associated myeloid cells.