Efferocytosis and the Story of "Find Me," "Eat Me," and "Don't Eat Me" Signaling in the Tumor Microenvironment

Abstract

The process of efferocytosis involves removal of dying or dead cells by phagocytosis. Another term "efferosome" is used which means a fluid-filled membrane vesicle which engulfs dead cells. The process of efferocytosis works in coordination with apoptosis because before the contents of apoptotic cells are bleached out, they are engulfed by efferosomes. Thus, the microenvironment is not polluted with toxic enzymes and oxidants. A defect in the apoptotic cell clearance may participate in autoimmunity and chronic inflammation for homeostasis and proper tissue development, for which removal of dead cells is essential. This also protects from chronic inflammation and autoimmunity. In different tumor types and other diseases, efferocytosis has been studied extensively and potential pathways identified. A few of the intermediates in different pathways, which create aggressive and tolerogenic tumor microenvironment, might be considered for therapeutic or interventional purposes. Since the key players in efferocytosis are macrophages and dendritic cells, development of antigen-dependent antitumor immunity is affected by efferocytosis. The literature analysis suggests that efferocytosis is an underappreciated immune checkpoint, perhaps one that might be therapeutically targeted in the setting of cancer. The current status of efferocytosis and its role in tumor microenvironment is discussed in this article.

Keywords: Apoptotic cells; Efferocytosis; Efferosome; Inflammation; Macrophage; Nitric oxide; Phagocytosis; Tumor microenvironment; microRNA.