Orchestration of Tumor-Associated Macrophages in the Tumor Cell-Macrophage-CD8⁺ T Cell Loop for Cancer Immunotherapy

The tumor microenvironment is densely populated with tumor-associated macrophages (TAMs), which exhibit various phenotypes at different stages of tumor progression. TAMs are highly plastic and intricately linked to the antitumor activity and functionality of CD8⁺ T cells. Tumor cells, TAMs and CD8⁺ T cells constitute a feedback loop that monitors the tumor immune surveillance. Modulation of several chief signaling pathways within TAMs can steer them towards either an immunoinflammatory or immunosuppressive state. This can be achieved indirectly through cancer therapies or by directly targeting TAMs. New detailed insights into the immunostimulatory reprogramming of TAMs inspire the design of novel combinatory strategies that can be extrapolated to bolster cancer immunotherapy.