Knockdown of Leptin Receptor Affects Macrophage Phenotype in the Tumor Microenvironment Inhibiting Breast Cancer Growth and Progression.

摘要: Aberrant leptin (Ob) signaling, a hallmark of obesity, has been recognized to influence breast cancer (BC) biology within the tumor microenvironment (TME). Here, we evaluated impact receptor (ObR) knockdown in affecting BC phenotype and mediating interaction between cells macrophages, most abundant immune TME. The stable ObR (ObR sh) ERα-positive ERα-negative turned into less aggressive one, as evidenced by vitro vivo models. In xenograft tumors co-culture experiments circulating monocytes cells, absence reduced recruitment also affected their cytokine mRNA expression profile. This was associated with decreased secretion monocyte chemoattractant protein-1 sh clones. loss Ob/ObR signaling modulated immunosuppressive TME, shown programmed death ligand 1/programmed cell protein 1/arginase 1. addition, observed increased phagocytic activity macrophages compared control Sh clones presence sh-derived conditioned medium. Our findings, addressing an innovative role modulating may open new avenues improve patient health care.