Targeting Macrophage Efferocytosis to Treat Chronic Inflammation in Cancer and Inflammaging

Efferocytosis, the process by which phagocytes clear apoptotic cells, is fundamental for maintaining physiological homeostasis. Inflammaging as a chronic and low-grade inflammatory state characteristic of aging is recognized as a significant contributor to tumor development. As crucial innate immune cells found in various tissues, macrophages are closely involved in both inflammaging and tumor. Accumulating evidence indicates that macrophage-mediated efferocytosis is closely linked to these processes, and its disruption can initiate or accelerate disease. Therefore, it is essential to elucidate the pivotal functions of macrophage efferocytosis in inflammaging and tumor biology to develop potential therapeutic strategies. Herein, this study first aims to uncover the crosstalk between inflammaging and tumor. We then investigate the mechanisms of macrophage efferocytosis, outlining its distinct functional phases and associated metabolic adaptations. The effects of efferocytosis on macrophage functions are also discussed. Furthermore, this study summarizes the prospective therapies treating inflammaging and tumor by modulating macrophage efferocytosis. Collectively, targeting macrophage efferocytosis represents a promising strategy for treating chronic inflammation-associated diseases, including tumor and inflammaging.