Tumor-associated myeloid cells: new understandings on their metabolic regulation and their influence in cancer immunotherapy

Tumor-associated myeloid cells (TAMCs), mainly represented by tumor-associated macrophages and myeloid-derived suppressor cells, can promote tumor growth directly, by favoring tumor cell proliferation and survival, and indirectly, by creating an immunosuppressive microenvironment. Myeloid cells are characterized by an extreme phenotypical and functional plasticity. Immunometabolism is now emerging as a crucial aspect of TAMCs skewing toward pro-tumoral activities. The metabolic re-education of myeloid cells is a new strategy to boost their antitumor effector functions. Several anticancer therapies targeting TAMCs are already under investigation. Nowadays, the hot topic of cancer immunotherapy is represented by immune checkpoint inhibitors. These drugs unrestrain T-cell-mediated tumor elimination by removing suppressive signals delivered by tumor-associated cells. The efficacy of immune checkpoint blockade can be enhanced using coordinated strategies to counteract the TAMCs-dependent impairment of immune adaptive responses. In the first part of the review, we will describe the association between metabolic reprogramming and TAMCs biological activities. In the second part, we will illustrate the potential of combination therapies associating TAMC-targeting drugs with immune checkpoint inhibitors.