Influencing immunity: role of extracellular vesicles in tumor immune checkpoint dynamics

Abstract

Immune checkpoint proteins (ICPs) serve as critical regulators of the immune system, ensuring protection against damage due to overly activated immune responses. However, within the tumor environment, excessive ICP activation weakens antitumor immunity. Despite the development of numerous immune checkpoint blockade (ICB) drugs in recent years, their broad application has been inhibited by uncertainties about their clinical efficacy. A thorough understanding of ICP regulation in the tumor microenvironment is essential for advancing the development of more effective and safer ICB therapies. Extracellular vesicles (EVs), which are pivotal mediators of cell–cell communication, have been extensively studied and found to play key roles in the functionality of ICPs. Nonetheless, a comprehensive review summarizing the current knowledge about the crosstalk between EVs and ICPs in the tumor environment is lacking. In this review, we summarize the interactions between EVs and several widely studied ICPs as well as their potential clinical implications, providing a theoretical basis for further investigation of EV-related ICB therapeutic approaches. In 1991, the finding of CTLA4 led to extensive studies on immune checkpoint proteins, key in controlling immune reactions. This review explores the role of extracellular vesicles—small particles released by cells carrying proteins, RNA, and lipids, affecting various cell functions—in immune checkpoint control. The research focuses on how EVs influence immune checkpoints, especially in cancer, where they can change immune cell function and affect therapy results. The authors aim to discover new treatment strategies by studying the interaction between EVs and immune checkpoints. This detailed review highlights the potential of targeting EV-related pathways to improve cancer treatment effectiveness and safety. The results emphasize the need for more research into EVs and immune checkpoints, potentially leading to significant progress in cancer treatment. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.