Tumor-derived extracellular vesicles: Hijacking T cell function through exhaustion

Abstract

Extracellular vesicles (EVs) play a vital role in intercellular communication within the tumor microenvironment (TME). These vesicles, secreted by tumor cells, contain proteins, lipids, and nucleic acids that significantly influence immune responses, particularly impacting T-cell function. In cancer, T cell dysfunction and exhaustion—marked by reduced proliferation, diminished cytokine production, and impaired cytotoxic activity—are key barriers to effective immune responses. Tumor-derived extracellular vesicles (TEVs) contribute to this dysfunction by carrying immunosuppressive molecules, such as transforming growth factor-beta (TGF-β) and various microRNAs (miRNAs). These TEV-mediated mechanisms promote T cell exhaustion and foster a broader immunosuppressive environment, enabling tumor progression and immune evasion. Furthermore, TEVs have been implicated in resistance to cancer immunotherapies, including immune checkpoint inhibitors and T cell therapies. Understanding the molecular pathways and cargoes within TEVs that drive T cell dysfunction is crucial for developing novel therapeutic strategies aimed at reinvigorating exhausted T cells, enhancing anti-tumor immunity, and improving cancer treatment outcomes.