Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines

Laura Gornati, Ivan Zanoni, Francesca Granucci, Laura Gornati, Ivan Zanoni, Francesca Granucci

Abstract

Vaccines represent the discovery of utmost importance for global health, due to both prophylactic action to prevent infections and therapeutic intervention in neoplastic diseases. Despite this, current vaccination strategies need to be refined to successfully generate robust protective antigen-specific memory immune responses. To address this issue, one possibility is to exploit the high efficiency of dendritic cells (DCs) as antigen-presenting cells for T cell priming. DCs functional plasticity allows shaping the outcome of immune responses to achieve the required type of immunity. Therefore, the choice of adjuvants to guide and sustain DCs maturation, the design of multifaceted vehicles, and the choice of surface molecules to specifically target DCs represent the key issues currently explored in both preclinical and clinical settings. Here, we review advances in DCs-based vaccination approaches, which exploit direct in vivo DCs targeting and activation options. We also discuss the recent findings for efficient antitumor DCs-based vaccinations and combination strategies to reduce the immune tolerance promoted by the tumor microenvironment.

Keywords: adjuvants; antigen delivery; dendritic cells; pattern recognition receptors; vaccination.

Figures

Figure 1
Figure 1
Dendritic cells (DCs) readapted taxonomy. Newly identified populations of blood human DCs are shown. DC1 subset is clearly distinct by the expression of CLEC9A, and it is specialized in cross-presentation of ags. DC2 and DC3 constitute the conventional DCs pool, even though they appear to be phenotypically slightly different and, upon stimulation with TLR ligands, their diversity emerges. DC4 is a population characterized by an upregulated Type I Interferon pathway for antiviral responses. DC5 has emerged as a new population whose specific functions are still unexplored. DC6 corresponds to the classic plasmacytoid DCs. These advances in the fine characterization of DCs in humans may shed light on the best subset to be targeted to incentivize the desired immune response.
Figure 2
Figure 2
Strategies of dendritic cells (DCs) targeting. Diverse approaches to deliver antigens to DCs are shown. (A) Recombinant antibody or single-chain variable fragment (scFv) specific for DC receptors are chemically conjugated with antigen and adjuvant molecules. scFv reduced dimension confers them higher tissue-penetrating properties. (B) Viral vector-based vaccines or naked DNA exploit the encoding machinery of DCs to translate antigens, adjuvants but also co-stimulatory molecules (“signal 2”) and cytokines (“signal 3”) increasing the activatory profile of DCs. Naked DNA could be delivered conjugated to nanoparticles (NPs) and liposomes. (C) Polymer-based NPs display physical and chemical properties that allow encapsulation or conjugation of antigens and adjuvants as well as ligands for specific DC receptors. Different polymer compositions provide diverse properties and dimension, allowing easy diffusion and/or retention in lymph node. (D) Liposomes allow both the encapsulation and intercalation in the phospholipid bilayer of antigens and adjuvants, depending on their chemical properties, as well as the functionalization of the surface with ligands of DC receptors.

References

    1. Russell CD. Eradicating infectious disease: can we and should we? Front Immunol (2011) 2:1–3.10.3389/fimmu.2011.00053
    1. Finlay BB, McFadden G. Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. Cell (2006) 124(4):767–82.10.1016/j.cell.2006.01.034
    1. Davenne T, McShane H. Why don’t we have an effective tuberculosis vaccine yet? Expert Rev Vaccines (2016) 15(8):1009–13.10.1586/14760584.2016.1170599
    1. Sahay B, Nguyen CQ, Yamamoto JK. Conserved HIV epitopes for an effective HIV vaccine. J Clin Cell Immunol (2017) 8(4):518.10.4172/2155-9899.1000518
    1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell (2011) 144(5):646–74.10.1016/j.cell.2011.02.013
    1. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature (1998) 392:245–52.10.1038/32588
    1. Steinman RM, Chon ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med (1973) 137:1142–62.10.1084/jem.137.5.1142
    1. Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lympoid organs of mice. II. Functional properties in vitro. J Exp Med (1974) 139:380–97.10.1084/jem.139.2.380
    1. Granot T, Senda T, Carpenter DJ, Matsuoka N, Weiner J, Gordon CL, et al. Dendritic cells display subset and tissue-specific maturation dynamics over human life. Immunity (2017) 46(3):504–15.10.1016/j.immuni.2017.02.019
    1. Guilliams M, Dutertre CA, Scott CL, McGovern N, Sichien D, Chakarov S, et al. Unsupervised high-dimensional analysis aligns dendritic cells across tissues and species. Immunity (2016) 45(3):669–84.10.1016/j.immuni.2016.08.015
    1. Elpek KG, Bellemare-Pelletier A, Malhotra D, Reynoso ED, Lukacs-Kornek V, DeKruyff RH, et al. Lymphoid organ-resident dendritic cells exhibit unique transcriptional fingerprints based on subset and site. PLoS One (2011) 6(8):e23921.10.1371/journal.pone.0023921
    1. Villani AC, Satija R, Reynolds G, Sarkizova S, Shekhar K, Fletcher J, et al. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science (2017) 356(6335):eaah4573.10.1126/science.aah4573
    1. Heidkamp GF, Sander J, Lehmann CHK, Heger L, Eissing N, Baranska A, et al. Human lymphoid organ dendritic cell identity is predominantly dictated by ontogeny, not tissue microenvironment. Sci Immunol (2016) 1(6):eaai7677.10.1126/sciimmunol.aai7677
    1. Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol (2013) 31(1):563–604.10.1146/annurev-immunol-020711-074950
    1. Alcántara-Hernández M, Leylek R, Wagar LE, Engleman EG, Keler T, Marinkovich MP, et al. High-dimensional phenotypic mapping of human dendritic cells reveals interindividual variation and tissue specialization. Immunity (2017) 47(6):1037–50.e6.10.1016/j.immuni.2017.11.001
    1. See P, Dutertre CA, Chen J, Günther P, McGovern N, Irac SE, et al. Mapping the human DC lineage through the integration of high-dimensional techniques. Science (2017) 356(6342):eaag3009.10.1126/science.aag3009
    1. Mildner A, Jung S. Development and function of dendritic cell subsets. Immunity (2014) 40(5):642–56.10.1016/j.immuni.2014.04.016
    1. Segura E, Valladeau-Guilemond J, Donnadieu M-H, Sastre-Garau X, Soumelis V, Amigorena S. Characterization of resident and migratory dendritic cells in human lymph nodes. J Exp Med (2012) 209(4):653–60.10.1084/jem.20111457
    1. Kashem SW, Igyarto BZ, Gerami-Nejad M, Kumamoto Y, Mohammed JA, Jarrett E, et al. Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation. Immunity (2015) 42(2):356–66.10.1016/j.immuni.2015.01.008
    1. Igyártó BZ, Haley K, Ortner D, Bobr A, Gerami-Nejad M, Edelson BT, et al. Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses. Immunity (2011) 35(2):260–72.10.1016/j.immuni.2011.06.005
    1. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell (2010) 140(6):805–20.10.1016/j.cell.2010.01.022
    1. Ivanov S, Scallan JP, Kim KW, Werth K, Johnson MW, Saunders BT, et al. CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability. J Clin Invest (2016) 126(4):1581–91.10.1172/JCI84518
    1. Förster R, Braun A, Worbs T. Lymph node homing of T cells and dendritic cells via afferent lymphatics. Trends Immunol (2012) 33(6):271–80.10.1016/j.it.2012.02.007
    1. Braun A, Worbs T, Moschovakis GL, Halle S, Hoffmann K, Bölter J, et al. Afferent lymph-derived T cells and DCs use different chemokine receptor CCR7-dependent routes for entry into the lymph node and intranodal migration. Nat Immunol (2011) 12(9):879–87.10.1038/ni.2085
    1. Itano AA, McSorley SJ, Reinhardt RL, Ehst BD, Ingulli E, Rudensky AY, et al. Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity. Immunity (2003) 19(1):47–57.10.1016/S1074-7613(03)00175-4
    1. Vitali C, Mingozzi F, Broggi A, Barresi S, Zolezzi F, Bayry J, et al. Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells. Blood (2012) 120(6):1237–45.10.1182/blood-2011-09-379776
    1. Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med (2001) 194(6):769–80.10.1084/jem.194.6.769
    1. Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol (2003) 21(1):685–711.10.1146/annurev.immunol.21.120601.141040
    1. Kolls JK. Th17 cells in mucosal immunity and tissue inflammation. Semin Immunopathol (2010) 32(1):1–2.10.1007/s00281-010-0198-8
    1. Zanoni I, Ostuni R, Capuano G, Collini M, Caccia M, Ronchi AE, et al. CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation. Nature (2009) 460(7252):264–8.10.1038/nature08118
    1. Chen M, Wang YH, Wang Y, Huang L, Sandoval H, Liu YJ, et al. Dendritic cell apoptosis in the maintenance of immune tolerance. Science (2006) 311(5764):1160–4.10.1126/science.1122545
    1. Stranges PB, Watson J, Cooper CJ, Choisy-Rossi CM, Stonebraker AC, Beighton RA, et al. Elimination of antigen-presenting cells and autoreactive T cells by Fas contributes to prevention of autoimmunity. Immunity (2007) 26(5):629–41.10.1016/j.immuni.2007.03.016
    1. Tubo NJ, Fife BT, Pagan AJ, Kotov DI, Goldberg MF, Jenkins MK. Most microbe-specific naïve CD4+ T cells produce memory cells during infection. Science (2016) 351(6272):511–5.10.1126/science.aad0483
    1. Wen Y, Shi Y. Alum: an old dog with new tricks. Emerg Microbes Infect (2016) 5(3):e25.10.1038/emi.2016.40
    1. Kool M, Pétrilli V, De Smedt T, Rolaz A, Hammad H, van Nimwegen M, et al. Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J Immunol (2008) 181(6):3755–9.10.4049/jimmunol.181.6.3755
    1. Li H, Willingham SB, Ting JP-Y, Re F. Cutting edge: inflammasome activation by alum and alum’s adjuvant effect are mediated by NLRP3. J Immunol (2008) 181(1):17–21.10.4049/jimmunol.181.1.17
    1. Franchi L, Núñez G. The Nlrp3 inflammasome is critical for aluminum hydroxide-mediated IL-1β secretion but dispensable for adjuvant activity. Eur J Immunol (2008) 38(8):2085–9.10.1002/eji.200838549
    1. Marichal T, Ohata K, Bedoret D, Mesnil C, Sabatel C, Kobiyama K, et al. DNA released from dying host cells mediates aluminum adjuvant activity. Nat Med (2011) 17(8):996–1002.10.1038/nm.2403
    1. Gavin AL, Hoebe K, Duong B, Ota T, Martin C, Beutler B, et al. Adjuvant-enhanced antibody receptor signaling. Science (2006) 314:1936–8.10.1126/science.1135299
    1. McKee AS, Munks MW, MacLeod MKL, Fleenor CJ, Van Rooijen N, Kappler JW, et al. Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity. J Immunol (2009) 183(7):4403–14.10.4049/jimmunol.0900164
    1. Khameneh HJ, Ho AWS, Spreafico R, Derks H, Quek HQY, Mortellaro A. The Syk–NFAT–IL-2 pathway in dendritic cells is required for optimal sterile immunity elicited by alum adjuvants. J Immunol (2017) 198(1):196–204.10.4049/jimmunol.1600420
    1. Knudsen NP, Olsen A, Buonsanti C, Follmann F, Zhang Y, Coler RN, et al. Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens. Sci Rep (2016) 6:1–13.10.1038/srep19570
    1. Cantisani R, Pezzicoli A, Cioncada R, Malzone C, De Gregorio E, D’Oro U, et al. Vaccine adjuvant MF59 promotes retention of unprocessed antigen in lymph node macrophage compartments and follicular dendritic cells. J Immunol (2015) 194(4):1717–25.10.4049/jimmunol.1400623
    1. Cioncada R, Maddaluno M, Vo HTM, Woodruff M, Tavarini S, Sammicheli C, et al. Vaccine adjuvant MF59 promotes the intranodal differentiation of antigen-loaded and activated monocyte-derived dendritic cells. PLoS One (2017) 12(10):e0185843.10.1371/journal.pone.0185843
    1. Szabo A, Gogolak P, Pazmandi K, Kis-Toth K, Riedl K, Wizel B, et al. The two-component adjuvant IC31® boosts type I interferon production of human monocyte-derived dendritic cells via ligation of endosomal TLRs. PLoS One (2013) 8(2).10.1371/journal.pone.0055264
    1. Sekiya T, Yamagishi J, Gray JHV, Whitney PG, Martinelli A, Zeng W, et al. PEGylation of a TLR2-agonist-based vaccine delivery system improves antigen trafficking and the magnitude of ensuing antibody and CD8+T cell responses. Biomaterials (2017) 137:61–72.10.1016/j.biomaterials.2017.05.018
    1. Halliday A, Turner JD, Guimarães A, Bates PA, Taylor MJ. The TLR2/6 ligand PAM2CSK4 is a Th2 polarizing adjuvant in Leishmania major and Brugia malayi murine vaccine models. Parasit Vectors (2016) 9(1):1–9.10.1186/s13071-016-1381-0
    1. Matsumoto M, Tatematsu M, Nishikawa F, Azuma M, Ishii N, Morii-Sakai A, et al. Defined TLR3-specific adjuvant that induces NK and CTL activation without significant cytokine production in vivo. Nat Commun (2015) 6:1–12.10.1038/ncomms7280
    1. Zhu Q, Egelston C, Gagnon S, Sui Y, Belyakov IM, Klinman DM, et al. Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in mice. J Clin Invest (2010) 120(2):607–16.10.1172/JCI39293
    1. Reed SG, Hsu FC, Carter D, Orr MT. The science of vaccine adjuvants: advances in TLR4 ligand adjuvants. Curr Opin Immunol (2016) 41:85–90.10.1016/j.coi.2016.06.007
    1. Lu Y, Swartz JR. Functional properties of flagellin as a stimulator of innate immunity. Sci Rep (2016) 6:1–11.10.1038/srep18379
    1. Buonsanti C, Balocchi C, Harfouche C, Corrente F, Galli Stampino L, Mancini F, et al. Novel adjuvant Alum-TLR7 significantly potentiates immune response to glycoconjugate vaccines. Sci Rep (2016) 6:1–12.10.1038/srep29063
    1. Bagnoli F, Fontana MR, Soldaini E, Mishra RP, Fiaschi L, Cartocci E, et al. Vaccine composition formulated with a novel TLR7-dependent adjuvant induces high and broad protection against Staphylococcus aureus. Proc Natl Acad Sci U S A (2015) 112(12):201424924.10.1073/pnas.1424924112
    1. Van Hoeven N, Fox CB, Granger B, Evers T, Joshi SW, Nana GI, et al. A Formulated TLR7/8 agonist is a flexible, highly potent and effective adjuvant for pandemic influenza vaccines. Sci Rep (2017) 7:1–15.10.1038/srep46426
    1. Song YC, Liu SJ. A TLR9 agonist enhances the anti-tumor immunity of peptide and lipopeptide vaccines via different mechanisms. Sci Rep (2015) 5:1–12.10.1038/srep12578
    1. Orr MT, Beebe EA, Hudson TE, Moon JJ, Fox CB, Reed SG, et al. A dual TLR agonist adjuvant enhances the immunogenicity and protective efficacy of the tuberculosis vaccine antigen ID93. PLoS One (2014) 9(1):e83884.10.1371/journal.pone.0083884
    1. Romero CD, Varma TK, Hobbs JB, Reyes A, Driver B, Sherwood ER. The toll-like receptor 4 agonist monophosphoryl lipid a augments innate host resistance to systemic bacterial infection. Infect Immun (2011) 79(9):3576–87.10.1128/IAI.00022-11
    1. Cui W, Joshi NS, Liu Y, Meng H, Kleinstein SH, Kaech SM. TLR4 ligands lipopolysaccharide and monophosphoryl lipid A differentially regulate effector and memory CD8+ T cell differentiation. J Immunol (2014) 192(9):4221–32.10.4049/jimmunol.1302569
    1. Hamdy S, Molavi O, Ma Z, Haddadi A, Alshamsan A, Gobti Z, et al. Co-delivery of cancer-associated antigen and toll-like receptor 4 ligand in PLGA nanoparticles induces potent CD8+T cell-mediated anti-tumor immunity. Vaccine (2008) 26(39):5046–57.10.1016/j.vaccine.2008.07.035
    1. Granucci F, Vizzardelli C, Pavelka N, Feau S, Persico M, Virzi E, et al. Inducible IL-2 production by dendritic cells revealed by global gene expression analysis. Nat Immunol (2001) 2(9):882–8.10.1038/ni0901-882
    1. Zanoni I, Granucci F. Regulation and dysregulation of innate immunity by NFAT signaling downstream of pattern recognition receptors (PRRs). Eur J Immunol (2012) 42(8):1924–31.10.1002/eji.201242580
    1. Wuest SC, Edwan JH, Martin JF, Han S, Perry JS, Cartagena CM, et al. A role for interleukin-2 trans-presentation in dendritic cell-mediated T cell activation in humans, as revealed by daclizumab therapy. Nat Med (2011) 17(5):604–9.10.1038/nm.2365
    1. Müller MR, Rao A. NFAT, immunity and cancer: a transcription factor comes of age. Nat Rev Immunol (2010) 10(9):645–56.10.1038/nri2818
    1. Goodridge HS, Simmons RM, Underhill DM. Dectin-1 stimulation by Candida albicans yeast or zymosan triggers NFAT activation in macrophages and dendritic cells. J Immunol (2007) 178(5):3107–15.10.4049/jimmunol.178.5.3107
    1. Greenblatt MB, Aliprantis A, Hu B, Glimcher LH. Calcineurin regulates innate antifungal immunity in neutrophils. J Exp Med (2010) 207(5):923–31.10.1084/jem.20092531
    1. Yonekawa A, Saijo S, Hoshino Y, Miyake Y, Ishikawa E, Suzukawa M, et al. Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria. Immunity (2014) 41(3):402–13.10.1016/j.immuni.2014.08.005
    1. Herbst S, Shah A, Mazon Moya M, Marzola V, Jensen B, Reed A, et al. Phagocytosis-dependent activation of a TLR9-BTK-calcineurin-NFAT pathway co-ordinates innate immunity to Aspergillus fumigatus. EMBO Mol Med (2015) 7(3):e201404556.10.15252/emmm.201404556
    1. Santus W, Barresi S, Mingozzi F, Broggi A, Orlandi I, Stamerra G, et al. Skin infections are eliminated by cooperation of the fibrinolytic and innate immune systems. Sci Immunol (2017) 2(15):eaan2725.10.1126/sciimmunol.aan2725
    1. Zanoni I, Spreafico R, Bodio C, Di Gioia M, Cigni C, Broggi A, et al. IL-15 cis presentation is required for optimal NK cell activation in lipopolysaccharide-mediated inflammatory conditions. Cell Rep (2013) 4(6):1235–49.10.1016/j.celrep.2013.08.021
    1. Granucci F, Zanoni I, Pavelka N, Van Dommelen SL, Andoniou CE, Belardelli F, et al. A contribution of mouse dendritic cell-derived IL-2 for NK cell activation. J Exp Med (2004) 200(3):287–95.10.1084/jem.20040370
    1. Zanoni I, Ostuni R, Barresi S, Di Gioia M, Broggi A, Costa B, et al. CD14 and NFAT mediate lipopolysaccharide- induced skin edema formation in mice. J Clin Invest (2012) 122(5):1747–57.10.1172/JCI60688
    1. Legler DF, Krause P, Scandella E, Singer E, Groettrup M. Prostaglandin E2 is generally required for human dendritic cell migration and exerts its effect via EP2 and EP4 receptors. J Immunol (2006) 176(2):966–73.10.4049/jimmunol.176.2.966
    1. Kastenmüller W, Torabi-Parizi P, Subramanian N, Lämmermann T, Germain RN. A spatially-organized multicellular innate immune response in lymph nodes limits systemic pathogen spread. Cell (2012) 150(6):1235–48.10.1016/j.cell.2012.07.021
    1. Gonzalez SF, Lukacs-Kornek V, Kuligowski MP, Pitcher LA, Degn SE, Kim YA, et al. Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes. Nat Immunol (2010) 11(5):427–34.10.1038/ni.1856
    1. Roozendaal R, Mempel TR, Pitcher LA, Gonzalez SF, Verschoor A, Mebius RE, et al. Conduits mediate transport of low-molecular-weight antigen to lymph node follicles. Immunity (2009) 30(2):264–76.10.1016/j.immuni.2008.12.014
    1. Gerner MY, Torabi-Parizi P, Germain RN. Strategically localized dendritic cells promote rapid T cell responses to lymph-borne particulate antigens. Immunity (2015) 42(1):172–85.10.1016/j.immuni.2014.12.024
    1. Gerner MY, Kastenmuller W, Ifrim I, Kabat J, Germain RN. Histo-cytometry: a method for highly multiplex quantitative tissue imaging analysis applied to dendritic cell subset microanatomy in lymph nodes. Immunity (2012) 37(2):364–76.10.1016/j.immuni.2012.07.011
    1. Iannacone M, Moseman EA, Tonti E, Bosurgi L, Junt T, Henrickson SE, et al. Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus. Nature (2010) 465(7301):1079–83.10.1038/nature09118
    1. Sixt M, Kanazawa N, Selg M, Samson T, Roos G, Reinhardt DP, et al. The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity (2005) 22(1):19–29.10.1016/j.immuni.2004.11.013
    1. Farrell HE, Davis-Poynter N, Bruce K, Lawler C, Dolken L, Mach M, et al. Lymph node macrophages restrict murine cytomegalovirus dissemination. J Virol (2015) 89(14):7147–58.10.1128/JVI.00480-15
    1. Frederico B, Chao B, Lawler C, May JS, Stevenson PG. Subcapsular sinus macrophages limit acute gammaherpesvirus dissemination. J Gen Virol (2015) 96(8):2314–27.10.1099/vir.0.000140
    1. Tomura M, Hata A, Matsuoka S, Shand FH, Nakanishi Y, Ikebuchi R, et al. Tracking and quantification of dendritic cell migration and antigen trafficking between the skin and lymph nodes. Sci Rep (2014) 4:1–11.10.1038/srep06030
    1. Kissenpfennig A, Henri S, Dubois B, Laplace-Builhé C, Perrin P, Romani N, et al. Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areasdistinct from slower migrating Langerhans cells. Immunity (2005) 22(5):643–54.10.1016/j.immuni.2005.04.004
    1. Radtke AJ, Kastenmüller W, Espinosa DA, Gerner MY, Tse SW, Sinnis P, et al. Lymph-node resident CD8a+ dendritic cells capture antigens from migratory malaria sporozoites and induce CD8+ T cell responses. PLoS Pathog (2015) 11(2):e1004637.10.1371/journal.ppat.1004637
    1. Iezzi G, Fröhlich A, Ernst B, Ampenberger F, Saeland S, Glaichenhaus N, et al. Lymph node resident rather than skin-derived dendritic cells initiate specific T cell responses after Leishmania major infection. J Immunol (2006) 177(2):1250–6.10.4049/jimmunol.177.2.1250
    1. Heath WR, Belz GT, Behrens GM, Smith CM, Forehan SP, Parish IA, et al. Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunol Rev (2004) 199:9–26.10.1111/j.0105-2896.2004.00142.x
    1. Thacker RI, Janssen EM. Cross-presentation of cell-associated antigens by mouse splenic dendritic cell populations. Front Immunol (2012) 3:41.10.3389/fimmu.2012.00041
    1. Brewitz A, Eickhoff S, Dähling S, Quast T, Bedoui S, Kroczek RA, et al. CD8+T cells orchestrate pDC-XCR1+dendritic cell spatial and functional cooperativity to optimize priming. Immunity (2017) 46(2):205–19.10.1016/j.immuni.2017.01.003
    1. Allan RS, Waithman J, Bedoui S, Jones CM, Villadangos JA, Zhan Y, et al. Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity (2006) 25(1):153–62.10.1016/j.immuni.2006.04.017
    1. Mount AM, Smith CM, Kupresanin F, Stoermer K, Heath WR, Belz GT. Multiple dendritic cell populations activate CD4+ T cells after viral stimulation. PLoS One (2008) 3(2):e1691.10.1371/journal.pone.0001691
    1. Bedoui S, Whitney PG, Waithman J, Eidsmo L, Wakim L, Caminschi I, et al. Cross-presentation of viral and self antigens by skin-derived CD103+dendritic cells. Nat Immunol (2009) 10(5):488–95.10.1038/ni.1724
    1. Kitano M, Yamazaki C, Takumi A, Ikeno T, Hemmi H, Takahashi N, et al. Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node. Proc Natl Acad Sci U S A (2016) 113(4):1044–9.10.1073/pnas.1513607113
    1. Waithman J, Zanker D, Xiao K, Oveissi S, Wylie B, Ng R, et al. Resident CD8+ and migratory CD103+ dendritic cells control CD8 T cell immunity during acute influenza infection. PLoS One (2013) 8(6):e66136.10.1371/journal.pone.0066136
    1. Haniffa M, Shin A, Bigley V, McGovern N, Teo P, See P, et al. Human tissues contain CD141hiCross-presenting dendritic cells with functional homology to mouse CD103+nonlymphoid dendritic cells. Immunity (2012) 37(1):60–73.10.1016/j.immuni.2012.04.012
    1. Edelson BT, KC W, Juang R, Kohyama M, Benoit LA, Klekotka PA, et al. Peripheral CD103 + dendritic cells form a unified subset developmentally related to CD8α + conventional dendritic cells. J Exp Med (2010) 207(4):823–36.10.1084/jem.20091627
    1. Dorner BG, Dorner MB, Zhou X, Opitz C, Mora A, Güttler S, et al. Selective expression of the chemokine receptor XCR1 on cross-presenting dendritic cells determines cooperation with CD8+ T cells. Immunity (2009) 31(5):823–33.10.1016/j.immuni.2009.08.027
    1. Ravindran R, Rusch L, Itano A, Jenkins MK, McSorley SJ. CCR6-dependent recruitment of blood phagocytes is necessary for rapid CD4 T cell responses to local bacterial infection. Proc Natl Acad Sci U S A (2007) 104(29):12075–80.10.1073/pnas.0701363104
    1. Van VQ, Lesage S, Bouguermouh S, Gautier P, Rubio M, Levesque M, et al. Expression of the self-marker CD47 on dendritic cells governs their trafficking to secondary lymphoid organs. EMBO J (2006) 25(23):5560–8.10.1038/sj.emboj.7601415
    1. Stoitzner P, Green LK, Jung JY, Price KM, Tripp CH, Malissen B, et al. Tumor immunotherapy by epicutaneous immunization requires Langerhans cells. J Immunol (2008) 180(3):1991–8.10.4049/jimmunol.180.3.1991
    1. Wang L, Bursch LS, Kissenpfennig A, Malissen B, Jameson SC, Hogquist KA. Langerin expressing cells promote skin immune responses under defined conditions. J Immunol (2008) 180(7):4722–7.10.4049/jimmunol.180.7.4722
    1. Seneschal J, Jiang X, Kupper TS. Langerin + dermal DC, but not Langerhans cells, are required for effective CD8-mediated immune responses after skin scarification with vaccinia virus. J Invest Dermatol (2014) 134(3):686–94.10.1038/jid.2013.418
    1. Kaplan DH. Langerhans cells: not your average dendritic cell. Trends Immunol (2010) 31(12):437.10.1016/j.it.2010.10.003
    1. Igyarto BZ, Jenison MC, Dudda JC, Roers A, Müller W, Koni PA, et al. Langerhans cells suppress contact hypersensitivity responses via cognate CD4 interaction and Langerhans cell-derived IL-10. J Immunol (2009) 183(8):5085–93.10.4049/jimmunol.0901884
    1. Mutyambizi K, Berger CL, Edelson RL. The balance between immunity and tolerance: the role of Langerhans cells. Cell Mol Life Sci (2009) 66(5):831–40.10.1007/s00018-008-8470-y
    1. Eickhoff S, Brewitz A, Gerner MY, Klauschen F, Komander K, Hemmi H, et al. Robust anti-viral immunity requires multiple distinct T cell-dendritic cell interactions. Cell (2015) 162(6):1322–37.10.1016/j.cell.2015.08.004
    1. Allenspach EJ, Lemos MP, Porrett PM, Turka LA, Laufer TM. Migratory and lymphoid-resident dendritic cells cooperate to efficiently prime naive CD4 T cells. Immunity (2008) 29(5):795–806.10.1016/j.immuni.2008.08.013
    1. Sen D, Forrest L, Kepler TB, Parker I, Cahalan MD. Selective and site-specific mobilization of dermal dendritic cells and Langerhans cells by Th1- and Th2-polarizing adjuvants. Proc Natl Acad Sci U S A (2010) 107(18):8334–9.10.1073/pnas.0912817107
    1. Antonialli R, Sulczewski FB, Amorim KNDS, Almeida BDS, Ferreira NS, Yamamoto MM, et al. CpG oligodeoxinucleotides and flagellin modulate the immune response to antigens targeted to CD8α+and CD8α- conventional dendritic cell subsets. Front Immunol (2017) 8:1727.10.3389/fimmu.2017.01727
    1. Rosalia RA, Cruz LJ, van Duikeren S, Tromp AT, Silva AL, Jiskoot W, et al. CD40-targeted dendritic cell delivery of PLGA-nanoparticle vaccines induce potent anti-tumor responses. Biomaterials (2015) 40:88–97.10.1016/j.biomaterials.2014.10.053
    1. Trumpfheller C, Finke JS, López CB, Moran TM, Moltedo B, Soares H, et al. Intensified and protective CD4 + T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine. J Exp Med (2006) 203(3):607–17.10.1084/jem.20052005
    1. Boscardin SB, Hafalla JC, Masilamani RF, Kamphorst AO, Zebroski HA, Rai U, et al. Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses. J Exp Med (2006) 203(3):599–606.10.1084/jem.20051639
    1. Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S, Soares H, et al. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med (2004) 199(6):815–24.10.1084/jem.20032220
    1. Beckman RA, Weiner LM, Davis HM. Antibody constructs in cancer therapy: protein engineering strategies to improve exposure in solid tumors. Cancer (2007) 109(2):170–9.10.1002/cncr.22402
    1. Granucci F, Prosperi D. Nanoparticles: “magic bullets” for targeting the immune system. Semin Immunol (2017) 34:1–2.10.1016/j.smim.2017.10.002
    1. Prosperi D, Colombo M, Zanoni I, Granucci F. Drug nanocarriers to treat autoimmunity and chronic inflammatory diseases. Semin Immunol (2017) 34:61–7.10.1016/j.smim.2017.08.010
    1. Boraschi D, Italiani P, Palomba R, Decuzzi P, Duschl A, Fadeel B, et al. Nanoparticles and innate immunity: new perspectives on host defence. Semin Immunol (2017) 34:33–51.10.1016/j.smim.2017.08.013
    1. Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, et al. Overall survival analysis of a phase II randomized controlled trial of a poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol (2010) 28(7):1099–105.10.1200/JCO.2009.25.0597
    1. Yang Z, Xu M, Jia Z, Zhang Y, Wang L, Zhang H, et al. A novel antigen delivery system induces strong humoral and CTL immune responses. Biomaterials (2017) 134:51–63.10.1016/j.biomaterials.2017.04.035
    1. Rincon-Restrepo M, Mayer A, Hauert S, Bonner DK, Phelps EA, Hubbell JA, et al. Vaccine nanocarriers: coupling intracellular pathways and cellular biodistribution to control CD4 vs CD8 T cell responses. Biomaterials (2017) 132:48–58.10.1016/j.biomaterials.2017.03.047
    1. Kim SY, Noh YW, Kang TH, Kim JE, Kim S, Um SH, et al. Synthetic vaccine nanoparticles target to lymph node triggering enhanced innate and adaptive antitumor immunity. Biomaterials (2017) 130:56–66.10.1016/j.biomaterials.2017.03.034
    1. Waeckerle-Men Y, Groettrup M. PLGA microspheres for improved antigen delivery to dendritic cells as cellular vaccines. Adv Drug Deliv Rev (2005) 57:475–82.10.1016/j.addr.2004.09.007
    1. Maji M, Mazumder S, Bhattacharya S, Choudhury ST, Sabur A, Shadab M, et al. A lipid based antigen delivery system efficiently facilitates MHC class-I antigen presentation in dendritic cells to stimulate CD8+T cells. Sci Rep (2016) 6:1–12.10.1038/srep27206
    1. Bachem A, Güttler S, Hartung E, Ebstein F, Schaefer M, Tannert A, et al. Superior antigen cross-presentation and XCR1 expression define human CD11c + CD141 + cells as homologues of mouse CD8 + dendritic cells. J Exp Med (2010) 207(6):1273–81.10.1084/jem.20100348
    1. Huysamen C, Willment JA, Dennehy KM, Brown GD. CLEC9A is a novel activation C-type lectin-like receptor expressed on BDCA3+ dendritic cells and a subset of monocytes. J Biol Chem (2008) 283(24):16693–701.10.1074/jbc.M709923200
    1. Poulin LF, Salio M, Griessinger E, Anjos-Afonso F, Craciun L, Chen JL, et al. Characterization of human DNGR-1 + BDCA3 + leukocytes as putative equivalents of mouse CD8α + dendritic cells. J Exp Med (2010) 207(6):1261–71.10.1084/jem.20092618
    1. Kroczek RA, Henn V. The role of XCR1 and its ligand XCL1 in antigen cross-presentation by murine and human dendritic cells. Front Immunol (2012) 3:1–5.10.3389/fimmu.2012.00014
    1. Schreibelt G, Klinkenberg LJ, Cruz LJ, Tacken PJ, Tel J, Kreutz M, et al. The C-type lectin receptor CLEC9A mediates antigen uptake and (cross-)presentation by human blood BDCA3+ myeloid dendritic cells. Blood (2012) 119(10):2284–92.10.1182/blood-2011-08-373944
    1. Li J, Ahmet F, Sullivan LC, Brooks AG, Kent SJ, De Rose R, et al. Antibodies targeting Clec9A promote strong humoral immunity without adjuvant in mice and non-human primates. Eur J Immunol (2015) 45(3):854–64.10.1002/eji.201445127
    1. Caminschi I, Ahmet F, Kitsoulis S, Teh JS, Lo JC, Rizzitelli A, et al. The dendritic cell subtype restricted C-type lectin Clec9A is a target for vaccine enhancement. Blood (2008) 112(8):3264–73.10.1182/blood-2008-05-155176
    1. Lahoud MH, Ahmet F, Kitsoulis S, Wan SS, Vremec D, Lee CN, et al. Targeting antigen to mouse dendritic cells via Clec9A induces potent CD4 T cell responses biased toward a follicular helper phenotype. J Immunol (2011) 187(2):842–50.10.4049/jimmunol.1101176
    1. Kato Y, Zaid A, Davey GM, Mueller SN, Nutt SL, Zotos D, et al. Targeting antigen to Clec9A primes follicular Th cell memory responses capable of robust recall. J Immunol (2015) 195(3):1006–14.10.4049/jimmunol.1500767
    1. Park H-Y, Light A, Lahoud MH, Caminschi I, Tarlinton DM, Shortman K. Evolution of B cell responses to Clec9A-targeted antigen. J Immunol (2013) 191(10):4919–25.10.4049/jimmunol.1301947
    1. Tullett KM, Leal Rojas IM, Minoda Y, Tan PS, Zhang JG, Smith C, et al. Targeting CLEC9A delivers antigen to human CD141+ DC for CD4+ and CD8+T cell recognition. JCI Insight (2016) 1(7):1–12.10.1172/jci.insight.87102
    1. Park HY, Tan PS, Kavishna R, Ker A, Lu J, Chan CEZ, et al. Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells. NPJ Vaccines (2017) 2(1):31.10.1038/s41541-017-0033-5
    1. Sancho D, Mourão-Sá D, Joffre OP, Schulz O, Rogers NC, Pennington DJ, et al. Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-type lectin. J Clin Invest (2008) 118(6):2098–110.10.1172/JCI34584
    1. Jiang W, Swiggard WJ, Heufler C, Peng M, Mirza A, Steinman RM, et al. The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature (1995) 375(6527):151–5.10.1038/375151a0
    1. Shrimpton RE, Butler M, Morel AS, Eren E, Hue SS, Ritter MA. CD205 (DEC-205): a recognition receptor for apoptotic and necrotic self. Mol Immunol (2009) 46(6):1229–39.10.1016/j.molimm.2008.11.016
    1. Kato M, McDonald KJ, Khan S, Ross IL, Vuckovic S, Chen K, et al. Expression of human DEC-205 (CD205) multilectin receptor on leukocytes. Int Immunol (2006) 18(6):857–69.10.1093/intimm/dxl022
    1. Mahnke K, Guo M, Lee S, Sepulveda H, Swain SL, Nussenzweig M, et al. The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex class II – positive lysosomal compartments. J Cell Biol (2000) 151(3):673–83.10.1083/jcb.151.3.673
    1. Guo M, Gong S, Maric S, Misulovin Z, Pack M, Mahnke K, et al. A monoclonal antibody to the DEC-205 endocytosis receptor on human dendritic cells. Hum Immunol (2000) 61(8):729–38.10.1016/S0198-8859(00)00144-0
    1. Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8 + T cell tolerance. J Exp Med (2002) 196(12):1627–38.10.1084/jem.20021598
    1. Tel J, Benitez-Ribas D, Hoosemans S, Cambi A, Adema GJ, Figdor CG, et al. DEC-205 mediates antigen uptake and presentation by both resting and activated human plasmacytoid dendritic cells. Eur J Immunol (2011) 41(4):1014–23.10.1002/eji.201040790
    1. Bozzacco L, Trumpfheller C, Siegal FP, Mehandru S, Markowitz M, Carrington M, et al. DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T cells in a spectrum of human MHC I haplotypes. Proc Natl Acad Sci U S A (2007) 104(4):1289–94.10.1073/pnas.0610383104
    1. Sartorius R, D’Apice L, Trovato M, Cuccaro F, Costa V, De Leo MG, et al. Antigen delivery by filamentous bacteriophage fd displaying an anti-DEC-205 single-chain variable fragment confers adjuvanticity by triggering a TLR9-mediated immune response. EMBO Mol Med (2015) 7(7):973–88.10.15252/emmm.201404525
    1. Sartorius R, Bettua C, D’Apice L, Caivano A, Trovato M, Russo D, et al. Vaccination with filamentous bacteriophages targeting DEC-205 induces DC maturation and potent anti-tumor T-cell responses in the absence of adjuvants. Eur J Immunol (2011) 41(9):2573–84.10.1002/eji.201141526
    1. Caminschi I, Meuter S, Heath WR. DEC-205 is a cell surface receptor for CpG oligonucleotides. Oncoimmunology (2013) 2(3):e23128.10.4161/onci.23128
    1. Becker T, Hartl FU, Wieland F. CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes. J Cell Biol (2002) 158(7):1277–85.10.1083/jcb.200208083
    1. Schjetne KW, Fredriksen AB, Bogen B. Delivery of antigen to CD40 induces protective immune responses against tumors. J Immunol (2007) 178(7):4169–76.10.4049/jimmunol.178.7.4169
    1. Xu H, Zhao G, Huang X, Ding Z, Wang J, Wang X, et al. CD40-expressing plasmid induces anti-CD40 antibody and enhances immune responses to DNA vaccination. J Gene Med (2010) 12(6):97–106.10.1002/jgm.1412
    1. Chen J, Zurawski G, Zurawski S, Wang Z, Akagawa K, Oh S, et al. A novel vaccine for mantle cell lymphoma based on targeting cyclin D1 to dendritic cells via CD40 hematology & oncology. J Hematol Oncol (2015) 8(1):1–15.10.1186/s13045-015-0131-7
    1. Mingozzi F, Spreafico R, Gorletta T, Cigni C, Di Gioia M, Caccia M, et al. Prolonged contact with dendritic cells turns lymph node-resident NK cells into anti-tumor effectors. EMBO Mol Med (2016) 8(9):1039–51.10.15252/emmm.201506164
    1. Dissanayake D, Murakami K, Tran MD, Elford AR, Millar DG, Ohashi PS. Peptide-pulsed dendritic cells have superior ability to induce immune-mediated tissue destruction compared to peptide with adjuvant. PLoS One (2014) 9(3):e92380.10.1371/journal.pone.0092380
    1. Bijker MS, van den Eeden SJ, Franken KL, Melief CJ, van der Burg SH, Offringa R. Superior induction of anti-tumor CTL immunity by extended peptide vaccines involves prolonged, DC-focused antigen presentation. Eur J Immunol (2008) 38:1033–42.10.1002/eji.200737995
    1. Rosalia RA, Quakkelaar ED, Redeker A, Khan S, Camps M, Drijfhout JW, et al. Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T-cell activation. Eur J Immunol (2013) 43:2554–65.10.1002/eji.201343324
    1. Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, Berends-van der Meer DM, Vloon AP, et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med (2009) 361:1838–47.10.1056/NEJMoa0810097
    1. Sabbatini P, Tsuji T, Ferran L, Ritter E, Sedrak C, Tuballes K, et al. Phase I trial of overlapping long peptides from a tumor self- antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients. Clin Cancer Res (2012) 18:6497–509.10.1158/1078-0432.CCR-12-2189
    1. Zeestraten EC, Speetjens FM, Welters MJ, Saadatmand S, Stynenbosch LF, Jongen R, et al. Addition of interferon-α to the p53-SLP V vaccine results in increased production of interferon- c in vaccinated colorectal cancer patients: a phase I/II clinical trial. Int J Cancer (2013) 132:1581–91.10.1002/ijc.27819
    1. Speetjens FM, Kuppen PJ, Welters MJ, Essahsah F, Voet van den Brink AM, Lantrua MG, et al. Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients T reated for metastatic colorectal cancer. Clin Cancer Res (2009) 15(3):1086–96.10.1158/1078-0432.CCR-08-2227
    1. Aarntzen EH, Schreibelt G, Bol K, Lesterhuis WJ, Croockewit AJ, de Wilt JH, et al. Vaccination with mRNA-electroporated dendritic cells induces robust tumor antigen-specific CD4+ and CD8+ T cells responses in stage III and IV melanoma patients. Clin Cancer Res (2012) 18(19):5460–70.10.1158/1078-0432.CCR-11-3368
    1. Bryson PD, Han X, Truong N, Wang P. Breast cancer vaccines delivered by dendritic cell-targeted lentivectors induce potent antitumor immune responses and protect mice from mammary tumor growth. Vaccine (2017) 35(43):5842–9.10.1016/j.vaccine.2017.09.017
    1. Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science (2015) 348(6230):69–74.10.1126/science.aaa4971
    1. Tanyi JL, Bobisse S, Ophir E, Tuyaerts S, Roberti A, Genolet R, et al. Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. Sci Transl Med (2018) 5931(April):1–15.10.1126/scitranslmed.aao5931
    1. Sahin U, Derhovanessian E, Miller M, Kloke BP, Simon P, Löwer M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature (2017) 547(7662):222–6.10.1038/nature23003
    1. Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature (2017) 547(7662):217–21.10.1038/nature22991
    1. Laxmanan S, Robertson SW, Wang E, Lau JS, David M, Mukhopadhyay D. Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways. Biochem Biophys Res Commun (2005) 334(1):193–8.10.1016/j.bbrc.2005.06.065
    1. Mimura K, Kono K, Takahashi A, Kawaguchi Y, Fujii H. Vascular endothelial growth factor inhibits the function of human mature dendritic cells mediated by VEGF receptor-2. Cancer Immunol Immunother (2007) 56:761–70.10.1007/s00262-006-0234-7
    1. Baghdadi M, Endo H, Takano A, Ishikawa K, Kameda Y, Wada H, et al. High co-expression of IL-34 and M-CSF correlates with tumor progression and poor survival in lung cancers. Sci Rep (2018) 8(1):418.10.1038/s41598-017-18796-8
    1. Kao JY, Gong Y, Chen C, Zheng Q-D, Chen J. Tumor-derived TGF-β reduces the efficacy of dendritic cell/tumor fusion vaccine. J Immunol (2018) 170:3806–11.10.4049/jimmunol.170.7.3806
    1. Zhao S, Wu D, Wu P, Wang Z, Huang J. Serum IL-10 predicts worse outcome in cancer patients: a meta-analysis. PLoS One (2015) 10(10):e0139598.10.1371/journal.pone.0139598
    1. Oft M. IL-10: master switch from tumor-promoting in flammation to antitumor immunity. Cancer Immunol Res (2014) 2:194–200.10.1158/2326-6066.CIR-13-0214
    1. Verronèse E, Delgado A, Valladeau-Guillemond J, Garin G, Guillemaut S, Tredan O, et al. Immune cell dysfunctions in breast cancer patients detected through whole blood multi-parametric flow cytometry assay. Oncoimmunology (2016) 5(3):e1100791.10.1080/2162402X.2015.1100791
    1. Imai K, Minamiya Y, Koyota S, Ito M, Saito H, Sato Y, et al. Inhibition of dendritic cell migration by transforming growth factor-b 1 increases tumor-draining lymph node metastasis. J Exp Clin Cancer Res (2012) 31(3):1–9.10.1186/1756-9966-31-3
    1. Schreibelt G, Bol KF, Westdorp H, Wimmers F, Aarntzen EH, Duiveman-de Boer T, et al. Effective clinical responses in metastatic melanoma patients after vaccination with primary myeloid dendritic cells. Clin Cancer Res (2016) 22(9):2155–66.10.1158/1078-0432.CCR-15-2205
    1. Anandasabapathy N, Feder R, Mollah S, Tse SW, Longhi MP, Mehandru S, et al. Classical Flt3L-dependent dendritic cells control immunity to protein vaccine. J Exp Med (2014) 211(9):1875–91.10.1084/jem.20131397
    1. Kreiter S, Diken M, Selmi A, Diekmann J, Attig S, Hüsemann Y, et al. FLT3 ligand enhances the cancer therapeutic potency of naked RNA vaccines. Cancer Res (2011) 71(19):6132–43.10.1158/0008-5472.CAN-11-0291
    1. Perez-Shibayama C, Gil-Cruz C, Nussbacher M, Allgäuer E, Cervantes-Barragan L, Züst R, et al. Dendritic cell-specific delivery of Flt3L by coronavirus vectors secures induction of therapeutic antitumor immunity. PLoS One (2013) 8(11):e81442.10.1371/journal.pone.0081442
    1. Antonios JP, Soto H, Everson RG, Orpilla J, Moughon D, Shin N, et al. PD-1 blockade enhances the vaccination-induced immune response in glioma. JCI Insight (2016) 1(10):e87059.10.1172/jci.insight.87059
    1. Zheng X, Koropatnick J, Chen D, Velenosi T, Ling H, Min W, et al. Silencing IDO in dendritic cells: a novel approach to enhance cancer immunotherapy in a murine breast cancer model. Int J Cancer (2013) 132:967–77.10.1002/ijc.27710
    1. Mentzer AJ, O’Connor D, Pollard AJ, Hill AVS. Searching for the human genetic factors standing in the way of universally effective vaccines. Philos Trans R Soc Lond B Biol Sci (2015) 370(1671):20140341–20140341.10.1098/rstb.2014.0341
    1. Tsang JS, Schwartzberg PL, Kotliarov Y, Biancotto A, Xie Z, Germain RN, et al. Global analyses of human immune variation reveal baseline predictors of postvaccination responses. Cell (2014) 157(2):499–513.10.1016/j.cell.2014.03.031

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