Polarization of tumor-associated macrophages by Chinese medicine intervention: mechanisms and applications

Abstract

Macrophage polarization is a spectrum of phenotypes and generally can be classified into two states: (1) classically activated or M1 macrophages, which can be driven by lipopolysaccharide (LPS) alone or in association with Th1 cytokines and produce pro-inflammatory cytokines such as TNF-α, IL-6 and, IL-12, and (2) alternatively activated M2 macrophages, which can be promoted by Th2 mediators IL-4 and IL-13 and produce anti-inflammatory cytokines such as TGF-β and IL-10. Current studies have found that the phenotypic switch between M1 and M2 macrophages governs the fate of an organ in inflammation or injury. The imbalance of M1/M2 polarization is closely involved in various pathological processes and is becoming a potential target for therapeutic strategies. Traditional Chinese medicine is an integrated healthcare system composed of many practices and is characterized by multi-target, multi-level, and coordinated intervention effects. Chinese medicines nowadays are applied to regulate phenotype polarization of macrophages to improve the microenvironment, thus ameliorating or even eliminating the symptoms. In this chapter, we will discuss the molecular mechanisms of macrophage polarization, their roles in health and disease, and the intervention with Chinese medicines to modulate the polarization of macrophages in tumor microenvironment (TME) for therapeutic purpose.