Extracellular vesicles (EVs) play a crucial role in intercellular communication as vehicles for the transport of membrane and cytosolic proteins, lipids, and nucleic acids including different RNAs. Dendritic cells (DCs)-derived EVs (DEVs), albeit variably, express major histocompatibility complex (MHC)-peptide complexes and co-stimulatory molecules on their surface that enable the interaction with other immune cells such as CD8⁺ T cells, and other ligands that stimulate natural killer (NK) cells, thereby instructing tumor rejection, and counteracting immune-suppressive tumor microenvironment. Malignant cells oppose this effect by secreting EVs bearing a variety of molecules that block DCs function. For instance, tumor-derived EVs (TDEVs) can impair myeloid cell differentiation resulting in myeloid-derived suppressor cells (MDSCs) generation. Hence, the unique composition of EVs makes them suitable candidates for the development of new cancer treatment approaches including prophylactic vaccine targeting oncogenic pathogens, cancer vaccines, and cancer immunotherapeutics. We offer a perspective from both cell sides, DCs, and tumor cells, on how EVs regulate the antitumor immune response, and how this translates into promising therapeutic options by reviewing the latest advancement in DEV-based cancer therapeutics.

Antigen cognate dendritic cell (DC)-T cell synaptic interactions drive activation of T cells and instruct DCs. Upon receiving CD4⁺ T cell help, post-synaptic DCs (psDCs) are licensed to generate CD8⁺ T cell responses. However, the cellular and molecular mechanisms that enable psDCs licensing remain unclear. Here, we describe that antigen presentation induces an upregulation of MHC-I protein molecules and increased lipid peroxidation on psDCs in vitro and in vivo. We also show that these events mediate DC licensing. In addition, psDC adoptive transfer enhances pathogen-specific CD8⁺ T responses and protects mice from infection in a CD8⁺ T cell-dependent manner. Conversely, depletion of psDCs in vivo abrogates antigen-specific CD8⁺ T cell responses during immunization. Together, our data show that psDCs enable CD8⁺ T cell responses in vivo during vaccination and reveal crucial molecular events underlying psDC licensing.

Understanding the fate of dendritic cells (DCs) after productive immune synapses (postsynaptic DCs) with T cells during antigen presentation has been largely neglected in favor of deciphering the nuances of T cell activation and memory generation. Here, we describe that postsynaptic DCs switch their transcriptomic signature, correlating with epigenomic changes including DNA accessibility and histone methylation. We focus on the chemokine receptor Ccr7 as a proof-of-concept gene that is increased in postsynaptic DCs. Consistent with our epigenomic observations, postsynaptic DCs migrate more efficiently toward CCL19 in vitro and display enhanced homing to draining lymph nodes in vivo. This work describes a previously unknown DC population whose transcriptomics, epigenomics, and migratory capacity change in response to their cognate contact with T cells.

The individual contribution of specific myeloid subsets such as CD1c ⁺ conventional DC (cDC) to perpetuation of rheumatoid arthritis (RA) pathology remains unclear. In addition, the specific innate sensors driving pathogenic activation of CD1c ⁺ cDC in patients with RA and their functional implications have not been characterized. Here, we assessed phenotypical, transcriptional, and functional characteristics of CD1c ⁺ and CD141 ⁺ cDC and monocytes from the blood and synovial fluid of patients with RA. Increased levels of CCR2 and the IgG receptor CD64 on circulating CD1c ⁺ cDC was associated with the presence of this DC subset in the synovial membrane in patients with RA. Moreover, synovial CD1c ⁺ cDC are characterized by increased expression of proinflammatory cytokines and high abilities to induce pathogenic IFN-γ ⁺ IL-17 ⁺ CD4 ⁺ T cells in vitro. Finally, we identified the crosstalk between Fcγ receptors and NLRC4 as a potential molecular mechanism mediating pathogenic activation, CD64 upregulation, and functional specialization of CD1c ⁺ cDC in response to dsDNA-IgG in patients with RA.

SUMMARY: CCT is required to regulate interorganelle contact sites through kinesin‐1 dynamics, modulating peroxisome and mitochondria activity, and ultimately controlling lipid cell content and metabolism.

Dendritic cells (DCs) bridge innate and adaptive immunity. Their main function is to present antigens to prime T cells and initiate and shape adaptive responses. Antigen presentation takes place through intimate contacts between the two cells, termed immune synapses (IS). During the formation of IS, information travels towards the T‐cell side to induce and tune its activation; but it also travels in reverse via engagement of membrane receptors and within extracellular vesicles transferred to the DC. Such reverse information transfer and its consequences on DC fate have been largely neglected. Here, we review the events and effects of IS‐mediated antigen presentation on DCs. In addition, we discuss novel technological advancements that enable monitoring DCs interactions with T lymphocytes, the main effects of DCs undergoing productive IS (postsynaptic DCs, or psDCs), and how reverse information transfer could be harnessed to modulate immune responses for therapeutic intervention.