Immune cell-derived extracellular vesicles (EVs) have increasingly become the focus of research due to their unique characteristics and bioinspired applications. They are lipid bilayer membrane nanosized vesicles harboring a range of immune cell-derived surface receptors and effector molecules from parental cells. Immune cell-derived EVs are important mediators of intercellular communication that regulate specific mechanisms of adaptive and innate immune responses. However, the mechanisms underlying the antitumor effects of EVs are still being explored. Importantly, immune cell-derived EVs have some unique features, including accessibility, storage, ability to pass through blood-brain and blood-tumor barriers, and loading of various effector molecules. Immune cell-derived EVs have been directly applied or engineered as potent antitumor vaccines or for the diagnosis of clinical diseases. More research applications involving genetic engineering, membrane engineering, and cargo delivery strategies have improved the treatment efficacy of EVs. Immune cell-derived EV-based therapies are expected to become a separate technique or to complement immunotherapy, radiotherapy, chemotherapy and other therapeutic modalities. This review aims to provide a comprehensive overview of the characteristics and functions of immune cell-derived EVs derived from adaptive (CD4⁺ T, CD8⁺ T and B cells) and innate immune cells (macrophages, NK cells, DCs, and neutrophils) and discuss emerging therapeutic opportunities and prospects in cancer treatment.

Tissue regeneration requires exogenous and endogenous signals, and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cells. The short-distance peripheral nerve showed a spontaneous regenerative phenomenon, which was initiated by the guiding role of macrophages. However, it cannot sufficiently restore long-distance nerve injury by itself. Based on this principle, we firstly constructed a proinflammatory model to prove that abnormal M2 expression reduce the guidance and repair effect of long-distance nerves. Furthermore, a bionic peptide hydrogel scaffold based on self-assembly was developed to envelop M2-derived regenerative cytokines and extracellular vesicles (EVs). The cytokines and EVs were quantified to mimic the guidance and regenerative microenvironment in a direct and mild manner. The bionic scaffold promoted M2 transformation in situ and led to proliferation and migration of Schwann cells, neuron growth and motor function recovery. Meanwhile, the peptide scaffold combined with CX3CL1 recruited more blood-derived M2 macrophages to promote long-distance nerve reconstruction. Overall, we systematically confirmed the important role of M2 in regulating and restoring the injury peripheral nerve. This bionic peptide hydrogel scaffold mimicked and remodeled the local environment for M2 transformation and recruitment, favoring long-distance peripheral nerve regeneration. It can help to explicate regulative effect of M2 may be a cause not just a consequence in nerve repair and tissue integration, which facilitating the development of pro-regenerative biomaterials.

Regeneration of neural tissue is limited following spinal cord injury (SCI). Successful regeneration of injured nerves requires the intrinsic regenerative capability of the neurons and a suitable microenvironment. However, the local microenvironment is damaged, including insufficient intraneural vascularization, prolonged immune responses, overactive immune responses, dysregulated bioenergetic metabolism and terminated bioelectrical conduction. Among them, the immune microenvironment formed by immune cells and cytokines plays a dual role in inflammation and regeneration. Few studies have focused on the role of the immune microenvironment in spinal cord regeneration. Here, we summarize those findings involving various immune cells (neutrophils, monocytes, microglia and T lymphocytes) after SCI. The pathological changes that occur in the local microenvironment and the function of immune cells are described. We also summarize and discuss the current strategies for treating SCI with tissue-engineered biomaterials from the perspective of the immune microenvironment.