DC-derived exosomes. have implications for diagnostics and the development of novel therapeutic strategies. This review discusses the role of exosomes in immunotherapy as carriers to stimulate an anti-cancer immune response and as predictive markers for immune CM 346 (Afobazole) activation; furthermore, it summarizes the mechanism and clinical application prospects of exosome-based immunotherapy in human cancer. and [25]. Therefore, as carriers to stimulate anti-cancer immune responses and deliver anti-cancer drugs, how exosomes could be utilized in immune therapy is important in regards to cancer progression and they CM 346 (Afobazole) have implications for diagnostics and the development of novel therapeutic strategies. In this review, we focused on the function and mechanism of exosome-based immunotherapy in human cancer, its significant therapeutic effect on cancer progression and the possibility of developing immunotherapeutic vaccines. The regulatory role of exosome-based immune responses The immune response refers to the body’s defensive response to harmful substances that are foreign or self-mutated. The immune response can be divided into the innate immune response and the adaptive immune response. Different types of immune cells are involved in the above nonspecific and specific immune responses. Phagocytes (including monocytes, macrophages and DCs) and natural killer (NK) cells are involved in innate immunity and constitute the first line of defense against pathogens; they also synergistically participate in the adaptive immune response. The adaptive acquired immune response utilizes T and B lymphocytes and their immunoglobulins and cytokines to produce a specific and heterogeneous response to invading microorganisms [26C28]. Currently, efforts are being made in the field of immunotherapy to find new low-toxicity inhibitors and better biosafety delivery vectors. Therefore, exosome-based therapy is a potential new approach to cancer immunotherapy because exosomes can be used as carriers to initiate anti-cancer immune responses and as a tool to deliver anti-cancer drugs [29] (Fig. ?(Fig.1).1). In the following chapter, the immune stimulatory and suppressive effects of exosomes secreted CM 346 (Afobazole) from different cells will be explained in detail (Fig. ?(Fig.22). Open in a separate window Fig. 1 Regulatory mechanisms of exosomes released by different cells on immune cells. Exosomes entry and exit into cells is indicated by black dotted lines. Exosomes are represented with the same color as the host cell. OE: overexpression. KD: PCDH8 knock-down Open in a separate window Fig. 2 The immune stimulatory and suppressive effects of cells-derived exosomes. This schematic displays the underlying mechanisms and functions of exosomes released from tumor cells and immune cells in the regulation of immune responses in tumor-bearing hosts Tumor-released exosomes Tumor-released exosomes have been widely studied in various types of cancer, such as renal cancer, hematological cancer, breast cancer and melanoma. Tumor-associated exosomes (TAEs) have essential roles in DCs participating in anti-cancer immune responses. Cooperating with DCs, exosomes from a rat pancreatic adenocarcinoma can activate tumor-antigen-specific cytotoxic T cell (CTL) responses and affect leukocyte proliferation through reduced CD44v6 upregulation and lck, ZAP70 and ERK1,2 phosphorylation [30]. A study of pancreatic cancer later found that miRNA-depleted exosome proteins may act as agonists for specifically activating DC/cytokine-induced killer cells (DC/CIK) [31]. In research on NSCLC, exosomes from Rab27a-overexpressing tumor cells have been shown to promote the maturation of DCs by upregulating major histocompatibility complex class I molecules (MHC II) and the costimulatory molecules CD80 and CD86, significantly promoting the proliferation and response of CD4+ T cells and [32]. More importantly, TAEs decreased the expression of PD-L1 on DCs, leading to the downregulation of Tregs [33]. In addition to upregulating MHC II and CM 346 (Afobazole) costimulatory molecules, TGF-1-silenced leukemia cell-derived exosomes promote DC function by inducing the secretion of interleukin (IL)-12p70 and tumor necrosis factor (TNF)- [34]. The purpose of cancer immunotherapy is to promote the activity of intracellular CTLs, assist in the initiation of tumor-specific CTLs in lymphoid organs, and establish effective and lasting anti-cancer immunity; thus, CD8+ T cells are.