ZDRCB2016018, QNRC2016453), the Specialized Project for Clinical Medicine of Jiangsu Province (Grant No

ZDRCB2016018, QNRC2016453), the Specialized Project for Clinical Medicine of Jiangsu Province (Grant No. exosomal PD-L1 may have the potential to be a target to overcome resistance to anti-PD-1/PD-L1 antibody therapy. Dendritic cell, Mesenchymal stem cell, Cytotoxic T lymphocyte, Natural killer, M2 macrophage, Tumor-associated macrophages cell, Regulatory T cell, Myeloid-derived suppressor cell, T helper Considering the origin of exosomes, TEXs may contain some tumor-associated antigens, including melan A, carcinoembryonic antigen and mesothelin [39, 40]. Thus, TEXs could be used to form a pool of tumor antigens to stimulate the anti-tumor response. Currently, TEXs have been widely used for the induction of anti-tumor responses in both murine models and clinical trials. A recent study reported that exosomes derived from heat-stressed tumor cells could induce the production of IL-6 by DCs and marcophage, which switches regulatory T cell into Th17 in tumor microenviroment in a HSP-70 dependent manner [20]. DCs have been proven to be a target for TEXs to enhance anti-tumor responses [21]. Research has found that EG7 tumor cell-derived exosomes transfer parental cell-associated antigen OVA and pMHC-I to DCs, which stimulate a stronger proliferation and differentiation of cytotoxic T lymphocytes (CTL) and generating a more strong OVA-specific antitumor immunity than control ones. Similar results were obtained in hepatocellular carcinoma (HCC) models and in other studies [21, 22]. Simultaneously, exosomes from TGF–silenced leukemia cells decrease the secretion of TGF- by DCs and Lomerizine dihydrochloride effectively promote OPD2 their maturation and function. Additionally, DCs transporting these exosomes facilitated the proliferation of CD4+ T cells and enhanced Lomerizine dihydrochloride the antigen-specific CTL responses [26, 27]. Interestingly, TEXs which exert a stable antitumor response are mostly based on targeting DCs. These provide a new idea for our future research. It has been reported that IEXs also contribute to enhancing the anti-tumor response. In addition, IEXs could alter the microenvironment suitable for tumors to suppress tumor growth. Recently, DC-derived exosomes (DEXs) have been recognized as a new class of vaccines for tumor therapy [35, 41]. In this research, Lu and coworkers found that Lomerizine dihydrochloride exosomes derived from a-fetoprotein (AFP)-expressing DCs could promote the antigen-specific immune response through elevating the levels of IFN- and interleukin-2 and reducing the expression of interleukin-10 and TGF-. Activated CD8+ T cell-derived extracellular vesicles are able to directly target mesenchymal tumor stromal cells to prevent tumor invasion and metastasis [34]. Exosomes released by NK cells have also been identified as having therapeutic effects. Both in vitro and in vivo experiments revealed that NK cell-derived exosomes could suppress the development of melanoma via their contents of TNF-, perforin and FasL [42]. In neuroblastoma (NB) tumors, exosomes derived from NK cells pretreated with NB cells increased the expression of natural killer cell receptors and enhanced the cytotoxicity of NK cells against NB tumors [43]. In addition to the exosomes mentioned above, exosomes derived from mesenchymal stem cells (MSCs) have also been reported to restrain tumor development [44]. MSC-derived exosomes have potent regulatory effects on immune responses including different immune cells, such as T cells and B cells [45]. Researchers have exhibited that human adipose Lomerizine dihydrochloride MSC-derived exosomes inhibit the proliferation and colony formation ability of A2780 and SKOV-3 human ovarian malignancy cells via inducing the expression of BAX and CASP3/9 while reducing the levels of BCL2 [46]. Interestingly, researchers have obtained similar results from human umbilical cord MSC-derived extracellular vesicles (EVs) [47]. Exosomes promote tumor progression Despite exosomes having anti-tumor effects as mentioned above, more.