The disbalance of LRP1 and SIRPα by psychological stress dampens the clearance of tumor cells by macrophages

The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies; however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stress-evoked tumor susceptibility, and the stress hormone glucocorticoid (GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor (low-density lipoprotein receptor-related protein-1, LRP1) and the "don't eat me" signal receptor (signal regulatory protein alpha, SIRPα). Further analysis revealed that GC led to a direct, glucocorticoid receptor (GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevated gene level of SIRPα by down-regulating miRNA-4695-3p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPα axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPα axis may serve as a potential therapeutic strategy for tumor treatment.

Research Progress on Relation Between CD47 and Immunotherapy on Lymphoma / 肿瘤防治研究

CD47 is a member of the immunoglobulin superfamily. It is expressed on various cells and tissues of human, but it is more expressed on tumor cells, especially in various hematopoietic tumors. The combination of CD47 expressed on tumor cells with signal regulator protein α (SIRPα) on macrophages inhibits the phagocytosis of tumors by macrophages. The reaction can lead to tumor immune escape. CD47 has become a new hot spot in tumor research. This article reviews the correlation between the structure and expression of CD47, CD47-SIRPα, CD47-targeting antibody drugs and lymphoma immunotherapy.