Macrophage-Based Therapeutic Strategies in Hematologic Malignancies

SIMPLE SUMMARY: Tumor-associated macrophages (TAMs) are the most prevalent immunosuppressive myeloid cells in the tumor microenvironment, playing significant functions in the regulation of tumor progression, invasion, and metastatic processes. The M1 and M2-polarized phenotypes of TAMs (immunostimulatory and immunosuppressive myeloid cells, respectively) have been potentially implicated in various cancers and autoimmune diseases. Understanding the precise function of TAMs could improve the assessment of the cancer response to T cell-based treatments and reverse tumor resistance to conventional therapies. Here, the involvement of TAMs in the development of various cancers, mainly hematologic tumors, and their pleiotropic activities are comprehensively discussed. ABSTRACT: Macrophages are types of immune cells, with ambivalent functions in tumor growth, which depend on the specific environment in which they reside. Tumor-associated macrophages (TAMs) are a diverse population of immunosuppressive myeloid cells that play significant roles in several malignancies. TAM infiltration in malignancies has been linked to a poor prognosis and limited response to treatments, including those using checkpoint inhibitors. Understanding the precise mechanisms through which macrophages contribute to tumor growth is an active area of research as targeting these cells may offer potential therapeutic approaches for cancer treatment. Numerous investigations have focused on anti-TAM-based methods that try to eliminate, rewire, or target the functional mediators released by these cells. Considering the importance of these strategies in the reversion of tumor resistance to conventional therapies and immune modulatory vaccination could be an appealing approach for the immunosuppressive targeting of myeloid cells in the tumor microenvironment (TME). The combination of reprogramming and TAM depletion is a special feature of this approach compared to other clinical strategies. Thus, the present review aims to comprehensively overview the pleiotropic activities of TAMs and their involvement in various stages of cancer development as a potent drug target, with a focus on hematologic tumors.