Efferocytosis and Its Associated Cytokines: A Light on Non-tumor and Tumor Diseases?

Abstract

Billions of cells undergo turnover and die via apoptosis throughout our lifetime. A prompt clearance of these apoptotic cells and debris by phagocytic cells, a process known as efferocytosis, is important in maintaining tissue homeostasis. Accordingly, impaired efferocytosis due to the defective clearance and disrupted stages can lead to a growing number of inflammation- and immune-related diseases. Although numerous studies have shown the mechanisms of efferocytosis, its role in disorders, such as non-tumor and tumor diseases, remains poorly understood. This review summarizes the processes and signal molecules in efferocytosis, and efferocytosis-related functions in non-tumor (e.g., atherosclerosis, lung diseases) and tumor diseases (e.g., breast cancer, prostate cancer), as well as describes the role of involved cytokines. Of note, there is a dual role of efferocytosis in the abovementioned disorders, and a paradoxical effect among non-tumor and tumor diseases in terms of inflammation resolution, immune response, and disease progression. Briefly, intact efferocytosis and cytokines promote tissue repair, while they contribute to tumor progression via the tumor microenvironment and macrophage politzerization. Additionally, this review provides potential targets associated with TAM (TYRO3, AXL, MERTK) receptors and cytokines, such as tumor necrosis factor α and CXCL5, suggesting potential novel therapeutic ways in treating diseases.