Exosomes in the hypoxic TME: from release, uptake and biofunctions to clinical applications

Abstract

Hypoxia is a remarkable trait of the tumor microenvironment (TME). When facing selective pressure, tumor cells show various adaptive characteristics, such as changes in the expression of cancer hallmarks (increased proliferation, suppressed apoptosis, immune evasion, and so on) and more frequent cell communication. Because of the adaptation of cancer cells to hypoxia, exploring the association between cell communication mediators and hypoxia has become increasingly important. Exosomes are important information carriers in cell-to-cell communication. Abundant evidence has proven that hypoxia effects in the TME are mediated by exosomes, with the occasional formation of feedback loops. In this review, we equally focus on the biogenesis and heterogeneity of cancer-derived exosomes and their functions under hypoxia and describe the known and potential mechanism ascribed to exosomes and hypoxia. Notably, we call attention to the size change of hypoxic cancer cell-derived exosomes, a characteristic long neglected, and propose some possible effects of this size change. Finally, jointly considering recent developments in the understanding of exosomes and tumors, we describe noteworthy problems in this field that urgently need to be solved for better research and clinical application.

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

“…Potential applications of exosomes as antitumor drug carriers are comprehensively discussed in a previous study by our group, which show utility as specific drug carriers for tumor-targeted therapy owing to low immunogenicity and biocompatibility [ 14 , 305 ]. However, specific conditions of TME (such as hypoxia or metabolism) may affect the morphology or heterogeneity of exosomes and Tu-Exo may exert tumorigenic effects [ 306 ]. Therefore, studies on changes in exosome properties in TME (including how Tu-Exos are involved in metabolic reprogramming to influence tumor progression) and avoidance of Tu-Exo-mediated tumor proliferation are essential to facilitate their successful clinical application.…”

KRAS mutant–driven SUMOylation controls extracellular vesicle transmission to trigger lymphangiogenesis in pancreatic cancer

“…EVs acquire various biological functions by packaging specific molecules during their biogenesis ( 43 ). It has been proposed that molecule packaging requires recognition by the ESCRT ( 44 ).…”

A New Hypoxia-Related Prognostic Risk Score (HPRS) Model Was Developed to Indicate Prognosis and Response to Immunotherapy for Lung Adenocarcinoma

“…TME is a complex network of immune cells, endothelial cells, fibroblasts, and various signal molecules [ 33 ]. Hypoxia is one of the most important factors in shaping TME [ 34 ]. In our research work, we explored the role of HPRS in TME in patients with LUAD.…”