Extracellular vesicles remodel tumor environment for cancer immunotherapy.

Tumor immunotherapy has transformed neoplastic disease management, yet low response rates and immune complications persist as major challenges. Extracellular vesicles including exosomes have emerged as therapeutic agents actively involved in a diverse range of pathological conditions. Mounting evidence suggests that alterations in the quantity and composition of extracellular vesicles (EVs) contribute to the remodeling of the immune-suppressive tumor microenvironment (TME), thereby influencing the efficacy of immunotherapy. This revelation has sparked clinical interest in utilizing EVs for immune sensitization. In this perspective article, we present a comprehensive overview of the origins, generation, and interplay among various components of EVs within the TME. Furthermore, we discuss the pivotal role of EVs in reshaping the TME during tumorigenesis and their specific cargo, such as PD-1 and non-coding RNA, which influence the phenotypes of critical immune cells within the TME. Additionally, we summarize the applications of EVs in different anti-tumor therapies, the latest advancements in engineering EVs for cancer immunotherapy, and the challenges encountered in clinical translation. In light of these findings, we advocate for a broader understanding of the impact of EVs on the TME, as this will unveil overlooked therapeutic vulnerabilities and potentially enhance the efficacy of existing cancer immunotherapies.

Radiotherapy remodels the tumor microenvironment for enhancing immunotherapeutic sensitivity.

Cancer immunotherapy has transformed traditional treatments, with immune checkpoint blockade being particularly prominent. However, immunotherapy has minimal benefit for patients in most types of cancer and is largely ineffective in some cancers (such as pancreatic cancer and glioma). A synergistic anti-tumor response may be produced through the combined application with traditional tumor treatment methods. Radiotherapy (RT) not only kills tumor cells but also triggers the pro-inflammatory molecules' release and immune cell infiltration, which remodel the tumor microenvironment (TME). Therefore, the combination of RT and immunotherapy is expected to achieve improved efficacy. In this review, we summarize the effects of RT on cellular components of the TME, including T cell receptor repertoires, different T cell subsets, metabolism, tumor-associated macrophages and other myeloid cells (dendritic cells, myeloid-derived suppressor cells, neutrophils and eosinophils). Meanwhile, non-cellular components such as lactate and extracellular vesicles are also elaborated. In addition, we discuss the impact of different RT modalities on tumor immunity and issues related to the clinical practice of combination therapy.

Roles of exosomal circRNAs in tumour immunity and cancer progression.

Tumour immunity plays an important role in the development of cancer. Tumour immunotherapy is an important component of antitumour therapy. Exosomes, a type of extracellular vesicle, act as mediators of intercellular communication and molecular transfer and play an essential role in tumour immunity. Circular RNAs (circRNAs) are a new type of noncoding RNA that are enriched within exosomes. In this review, we describe the effects of exosomal circRNAs on various immune cells and the mechanisms of these effects, including macrophages, neutrophils, T cells, and Natural killer (NK) cells. Next, we elaborate on the latest progress of exosome extraction. In addition, the function of exosomal circRNAs as a potential prognostic and drug sensitivity marker is described. We present the great promise of exosomal circRNAs in regulating tumour immunity, predicting patient outcomes, and evaluating drug efficacy.