Macrophage lncRNAs in cancer development: Long-awaited therapeutic targets

Abstract

In the tumor microenvironment, the interplay among macrophages, cancer cells, and endothelial cells is multifaceted. Tumor-associated macrophages (TAMs), which often exhibit an M2 phenotype, contribute to tumor growth and angiogenesis, while cancer cells and endothelial cells reciprocally influence macrophage behavior. This complex interrelationship highlights the importance of targeting these interactions for the development of novel cancer therapies aimed at disrupting tumor progression and angiogenesis. Accumulating evidence underscores the indispensable involvement of lncRNAs in shaping macrophage functionality and contributing to the development of cancer. Animal studies have further validated the therapeutic potential of manipulating macrophage lncRNA activity to ameliorate disease severity and reduce morbidity rates. This review provides a survey of our current understanding of macrophage-associated lncRNAs, with a specific emphasis on their molecular targets and their regulatory impact on cancer progression. These lncRNAs predominantly govern macrophage polarization, favoring the dominance of M2 macrophages or TAMs. Exosomes or extracellular vesicles mediate lncRNA transfer between macrophages and cancer cells, affecting cellular functions of each other. Moreover, this review presents therapeutic strategies targeting cancer-associated lncRNAs. The insights and findings presented in this review pertaining to macrophage lncRNAs can offer valuable information for the development of treatments against cancer.

Keywords: Cancer; Exosome; M2 macrophage; Macrophage polarization; TAM; Therapeutic targets; lncRNA.