@article{7c063b93a20f4cefb2ab838cc1e06e49,
title = "Re-Emergence of Dendritic Cell Vaccines for Cancer Treatment",
abstract = "Dendritic cells (DCs) are essential in immunity owing to their role in activating T cells, thereby promoting antitumor responses. Tumor cells, however, hijack the immune system, causing T cell exhaustion and DC dysfunction. Tumor-induced T cell exhaustion may be reversed through immune checkpoint blockade (ICB); however, this treatment fails to show clinical benefit in many patients. While ICB serves to reverse T cell exhaustion, DCs are still necessary to prime, activate, and direct the T cells to target tumor cells. In this review we provide a brief overview of DC function, describe mechanisms by which DC functions are disrupted by the tumor microenvironment, and highlight recent developments in DC cancer vaccines.",
keywords = "cancer, dendritic cells, immune suppression, immunotherapy, tumor microenvironment, vaccines",
author = "Mansi Saxena and Nina Bhardwaj",
note = "Funding Information: This work was supported by the National Institutes of Health (RO1CA201189, R01CA180913 and R01AI081848), Cancer Research Institute and the Melanoma Research Alliance. NB is a member of the Parker Institute for Cancer Immunotherapy, which supported Icahn School of Medicine at Mount Sinai, NY, Cancer Immunotherapy Program. Alarmins endogenous ligands secreted by dying, necrotic, or stressed tumor cells that can activate immune cells even in the absence of infection. Examples of activating alarmins include HMGB1, HSPs, and ATP [1] . Several RNA species are now emerging as novel alarmins. Long non-coding RNA such as HSATII (upregulated in human epithelial cancers such as pancreatic cancer) can act as alarmins by inducing the secretion of IL-12 and TNF-α in human monocyte-derived dendritic cells (DCs) [132] . Similarly, tumor-secreted exosomes laden with non-coding Y RNA, hY4, were demonstrated to activate Toll-like receptor 7 (TLR-7) on monocytes and elicit inflammation [133] . Furthermore, pharmacological epigenetic modulators have been shown to enhance expression of {\textquoteleft}activating{\textquoteright} alarmins such as double-stranded (ds) RNA encoded by endogenous retroviruses [134,135] . Antigen cross-presentation a unique ability of DCs to internalize exogenous antigens into phagosomes and present them on MHC-I molecules to activate CD8 + T cells [136,137] . Interestingly, TLR-4 engagement has been shown to induce cross-presentation by facilitating lysosome clustering and delaying cargo degradation in phagosomes [138,139] . In addition, early TLR stimulation has also been reported to promote transfer of reserve MHC-I molecules from the endosomal recycling compartment to the phagosomes to support cross-presentation [140] . Cross-dressing a cellular process through which receiver lymph node (LN) DCs may directly take up pre-antigen-loaded MHC-I complexes from donor migratory DCs and express this complex on their cell surface [141] . Fms-related tyrosine kinase 3 ligand (Flt3L) a cytokine necessary for DC mobilization and proliferation. Indoleamine 2,3-dioxygenase (IDO) an enzyme that induces depletion of tryptophan, a metabolite important for T cell activation. Microsatellite instability (MSI) manifested as aberrant repetitions in DNA sequences that are introduced when the tumor cells harbor mutations in DNA mismatch repair (MMR) genes. Monocyte-derived dendritic cells (MoDCs) are generated by isolating CD14 + monocytes from patient blood and differentiating these into immature DCs under the influence of IL-4 and GM-CSF. Sipuleucel-T a vaccine comprising an enriched preparation of white cells containing a significant fraction of antigen-presenting cells (APCs), including DCs. These are pulsed with prostatic acid phosphatase (PAP) fused with GM-CSF (PA2024) ex vivo , and are then reintroduced in the patient intravenously to induce immunity [142,143] . Vascular endothelial growth factor (VEGF) a cytokine induced in response to stresses such as hypoxia, under the regulation of hypoxia-inducible factor, and aids in tissue healing and wound repair. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = feb,
doi = "10.1016/j.trecan.2017.12.007",
language = "English",
volume = "4",
pages = "119--137",
journal = "Trends in Cancer",
issn = "2405-8033",
publisher = "Cell Press",
number = "2",
}