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Review

Dendritic Cell-Based Vaccines Against Cancer: Challenges, Advances and Future Opportunities

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References

  • Adiko AC, Babdor J, Gutierrez-Martinez E, Guermonprez P, Saveanu L. 2015. Intracellular transport routes for MHC I and their relevance for antigen cross-presentation. Front Immunol. 6:335.
  • Alcantara-Hernandez M, Leylek R, Wagar LE, Engleman EG, Keler T, Marinkovich MP, Davis MM, Nolan GP, Idoyaga J. 2017. High-dimensional phenotypic mapping of human dendritic cells reveals interindividual variation and tissue specialization. Immunity. 47(6):1037–50 e6.
  • Alculumbre SG, Saint-Andre V, Di Domizio J, Vargas P, Sirven P, Bost P, Maurin M, Maiuri P, Wery M, Roman MS, et al. 2018. Diversification of human plasmacytoid predendritic cells in response to a single stimulus. Nat Immunol. 19(1):63–75.
  • Alfei F, Ho PC, Lo WL. 2021. Decision- making in tumors governs T cell anti-tumor immunity. Oncogene. 40(34):5253–61.
  • Andersen BM, Ohlfest JR. 2012. Increasing the efficacy of tumor cell vaccines by enhancing cross priming. Cancer Lett. 325(2):155–64.
  • Anderson DA, 3rd, Dutertre CA, Ginhoux F, Murphy KM. 2021. Genetic models of human and mouse dendritic cell development and function. Nat Rev Immunol. 21(2):101–15.
  • Andre F, Chaput N, Schartz NE, Flament C, Aubert N, Bernard J, Lemonnier F, Raposo G, Escudier B, Hsu DH, et al. 2004. Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells. J Immunol. 172(4):2126–36.
  • Aspord C, Charles J, Leccia MT, Laurin D, Richard MJ, Chaperot L, Plumas J. 2010. A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells. PLoS One. 5(5):e10458.
  • Aspord C, Leccia MT, Charles J, Plumas J. 2013. Plasmacytoid dendritic cells support melanoma progression by promoting Th2 and regulatory immunity through OX40L and ICOSL. Cancer Immunol Res. 1(6):402–15.
  • Aspord C, Leccia MT, Charles J, Plumas J. 2014. Melanoma hijacks plasmacytoid dendritic cells to promote its own progression. Oncoimmunology. 3(1):e27402.
  • Aspord C, Leccia MT, Salameire D, Laurin D, Chaperot L, Charles J, Plumas J. 2012. HLA-A(*)0201(+) plasmacytoid dendritic cells provide a cell-based immunotherapy for melanoma patients. J Invest Dermatol. 132(10):2395–406.
  • Bachem A, Guttler S, Hartung E, Ebstein F, Schaefer M, Tannert A, Salama A, Movassaghi K, Opitz C, Mages HW, et al. 2010. Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells. J Exp Med. 207(6):1273–81.
  • Balan S, Dalod M. 2016. In vitro Generation of human XCR1(+) dendritic cells from CD34(+) hematopoietic progenitors. Methods Mol Biol. 1423:19–37.
  • Balan S, Ollion V, Colletti N, Chelbi R, Montanana-Sanchis F, Liu H, Vu Manh TP, Sanchez C, Savoret J, Perrot I, et al. 2014. Human XCR1+ dendritic cells derived in vitro from CD34+ progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells. J Immunol. 193(4):1622–35.
  • Baldin AV, Savvateeva LV, Bazhin AV, Zamyatnin AA, Jr. 2020. Dendritic cells in anticancer vaccination: rationale for ex vivo loading or in vivo targeting. Cancers (Basel). 12(3). doi:10.3390/cancers12030590
  • Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, Taquet S, Coquery S, Wittkowski KM, Bhardwaj N, et al. 2001. Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res. 61(17):6451–58.
  • Bandola-Simon J, Roche PA. 2018. Dysfunction of antigen processing and presentation by dendritic cells in cancer. Mol Immunol. 113:31–37.
  • Bell BM, Kirk ID, Hiltbrunner S, Gabrielsson S, Bultema JJ. 2016. Designer exosomes as next-generation cancer immunotherapy. Nanomedicine. 12(1):163–69.
  • Besse B, Charrier M, Lapierre V, Dansin E, Lantz O, Planchard D, Le Chevalier T, Livartoski A, Barlesi F, Laplanche A, et al. 2016. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology. 5(4):e1071008.
  • Bevan MJ. 1976a. Cross-Priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. J Exp Med. 143(5):1283–88.
  • Bevan MJ. 1976b. Minor H antigens introduced on H-2 different stimulating cells cross-react at the cytotoxic T cell level during in vivo priming. J Immunol. 117(6):2233–38.
  • Bhardwaj N, Friedlander PA, Pavlick AC, Ernstoff MS, Gastman BR, Hanks BA, Curti BD, Albertini MR, Luke JJ, Blazquez AB, et al. 2020. Flt3 ligand augments immune responses to anti-DEC-205-NY-ESO-1 vaccine through expansion of dendritic cell subsets. Nat Cancer. 1(12):1204–17.
  • Binnewies M, Mujal AM, Pollack JL, Combes AJ, Hardison EA, Barry KC, Tsui J, Ruhland MK, Kersten K, Abushawish MA, et al. 2019. Unleashing type-2 dendritic cells to drive protective antitumor CD4(+) T cell immunity. Cell. 177(3):556–71 e16.
  • Blass E, Ott PA. 2021. Advances in the development of personalized neoantigen-based therapeutic cancer vaccines. Nat Rev Clin Oncol. 18(4):215–29.
  • Bluth MJ, Zaba LC, Moussai D, Suarez-Farinas M, Kaporis H, Fan L, Pierson KC, White TR, Pitts-Kiefer A, Fuentes-Duculan J, et al. 2009. Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of T-cell proliferation. J Invest Dermatol. 129(10):2451–62.
  • Bol KF, Schreibelt G, Rabold K, Wculek SK, Schwarze JK, Dzionek A, Teijeira A, Kandalaft LE, Romero P, Coukos G, et al. 2019. The clinical application of cancer immunotherapy based on naturally circulating dendritic cells. J Immunother Cancer. 7(1):109.
  • Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S, Soares H, Brimnes MK, Moltedo B, Moran TM, Steinman RM. 2004. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med. 199(6):815–24.
  • Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM. 2002. 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. 196(12):1627–38.
  • Bottcher JP, Bonavita E, Chakravarty P, Blees H, Cabeza-Cabrerizo M, Sammicheli S, Rogers NC, Sahai E, Zelenay S, Reis E Sousa C. 2018. NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell. 172(5):1022–37 e14.
  • Bourdely P, Anselmi G, Vaivode K, Ramos RN, Missolo-Koussou Y, Hidalgo S, Tosselo J, Nunez N, Richer W, Vincent-Salomon A, et al. 2020. Transcriptional and functional analysis of CD1c(+) human dendritic cells identifies a CD163(+) subset priming CD8(+)CD103(+) T cells. Immunity. 53(2):335–52 e8.
  • Brewitz A, Eickhoff S, Dahling S, Quast T, Bedoui S, Kroczek RA, Kurts C, Garbi N, Barchet W, Iannacone M, et al. 2017. CD8(+) T cells Orchestrate pDC-XCR1(+) dendritic cell spatial and functional cooperativity to optimize priming. Immunity. 46(2):205–19.
  • Brown CC, Gudjonson H, Pritykin Y, Deep D, Lavallee VP, Mendoza A, Fromme R, Mazutis L, Ariyan C, Leslie C, et al. 2019. Transcriptional basis of mouse and human dendritic cell heterogeneity. Cell. 179(4):846–63 e24.
  • Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, Barczak A, Rosenblum MD, Daud A, Barber DL, et al. 2014. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell. 26(5):638–52.
  • Bryant C, Fromm PD, Kupresanin F, Clark G, Lee K, Clarke C, Silveira PA, Suen H, Brown R, Newman E, et al. 2016. A CD2 high-expressing stress-resistant human plasmacytoid dendritic-cell subset. Immunol Cell Biol. 94(5):447–57.
  • Bryant CE, Sutherland S, Kong B, Papadimitrious MS, Fromm PD, Hart DNJ. 2019. Dendritic cells as cancer therapeutics. Seminars Cell Develop Biol. 86:77–88.
  • Calmeiro J, Carrascal M, Gomes C, Falcao A, Cruz MT, Neves BM. 2019. Biomaterial-Based platforms for in situ dendritic cell programming and their use in antitumor immunotherapy. J Immunother Cancer. 7(1):238.
  • Calmeiro J, Carrascal MA, Tavares AR, Ferreira DA, Gomes C, Falcao A, Cruz MT, Neves BM. 2020. Dendritic cell vaccines for cancer immunotherapy: the role of human conventional type 1 dendritic cells. Pharmaceutics. 12(2):158.
  • Caminschi I, Maraskovsky E, Heath WR. 2012. Targeting dendritic cells in vivo for cancer therapy. Front Immunol. 3:13.
  • Campana S, De Pasquale C, Carrega P, Ferlazzo G, Bonaccorsi I. 2015. Cross-dressing: an alternative mechanism for antigen presentation. Immunol Lett. 168(2):349–54.
  • Cao T, Ueno H, Glaser C, Fay JW, Palucka AK, Banchereau J. 2007. Both Langerhans cells and interstitial DC cross-present melanoma antigens and efficiently activate antigen-specific CTL. Eur J Immunol. 37(9):2657–67.
  • Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, Ly A, Lie WR, Hildebrand WH, Mardis ER, et al. 2015. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 348(6236):803–08.
  • Chaperot L, Blum A, Manches O, Lui G, Angel J, Molens JP, Plumas J. 2006. Virus or TLR agonists induce TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells. J Immunol. 176(1):248–55.
  • Charles J, Chaperot L, Hannani D, Bruder Costa J, Templier I, Trabelsi S, Gil H, Moisan A, Persoons V, Hegelhofer H, et al. 2020. An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial. Oncoimmunology. 9(1):1738812.
  • Charles J, Chaperot L, Revol B, Baudin M, Mouret S, Hamon A, Leccia MT, Plumas J, Aspord C. 2018. The avidity of tumor-specific T cells amplified by a plasmacytoid dendritic cell-based assay can predict the clinical evolution of melanoma patients. Pigment Cell Melanoma Res. 31(1):82–94.
  • Chen L, Fabian KL, Taylor JL, Storkus WJ. 2013. Therapeutic use of dendritic cells to promote the extranodal priming of anti-tumor immunity. Front Immunol. 4:388.
  • Chen DS, Mellman I. 2013. Oncology meets immunology: the cancer-immunity cycle. Immunity. 39(1):1–10.
  • Chrisikos TT, Zhou Y, Slone N, Babcock R, Watowich SS, Li HS. 2019. Molecular regulation of dendritic cell development and function in homeostasis, inflammation, and cancer. Mol Immunol. 110:24–39.
  • Chung DJ, Sharma S, Rangesa M, DeWolf S, Elhanati Y, Perica K, Young JW. 2022. Langerhans dendritic cell vaccine bearing mRNA-encoded tumor antigens induces antimyeloma immunity after autotransplant. Blood Adv. 6(5):1547–58.
  • Cisse B, Caton ML, Lehner M, Maeda T, Scheu S, Locksley R, Holmberg D, Zweier C, den Hollander NS, Kant SG, et al. 2008. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell. 135(1):37–48.
  • Cohn L, Chatterjee B, Esselborn F, Smed-Sorensen A, Nakamura N, Chalouni C, Lee BC, Vandlen R, Keler T, Lauer P, et al. 2013. Antigen delivery to early endosomes eliminates the superiority of human blood BDCA3+ dendritic cells at cross presentation. J Exp Med. 210(5):1049–63.
  • Cohn L, Delamarre L. 2014. Dendritic cell-targeted vaccines. Front Immunol. 5:255.
  • Collin M, Bigley V. 2018. Human dendritic cell subsets: an update. Immunology. 154(1):3–20.
  • Collin M, McGovern N, Haniffa M. 2013. Human dendritic cell subsets. Immunology. 140(1):22–30.
  • Cueto FJ, Sancho D. 2021. The Flt3L/Flt3 axis in dendritic cell biology and cancer immunotherapy. Cancers (Basel). 13(7):1525.
  • Cytlak U, Resteu A, Pagan S, Green K, Milne P, Maisuria S, McDonald D, Hulme G, Filby A, Carpenter B, et al. 2020. Differential IRF8 transcription factor requirement defines two pathways of dendritic cell development in humans. Immunity. 53(2):353–70 e8.
  • Davis ID, Chen Q, Morris L, Quirk J, Stanley M, Tavarnesi ML, Parente P, Cavicchiolo T, Hopkins W, Jackson H, et al. 2006. Blood dendritic cells generated with Flt3 ligand and CD40 ligand prime CD8+ T cells efficiently in cancer patients. J Immunother (1991). 29(5):499–511.
  • Davis ID, Quirk J, Morris L, Seddon L, Tai TY, Whitty G, Cavicchiolo T, Ebert L, Jackson H, Browning J, et al. 2017. A pilot study of peripheral blood BDCA-1 (Cd1c) positive dendritic cells pulsed with NY-ESO-1 ISCOMATRIX adjuvant. Immunotherapy. 9(3):249–59.
  • De Vries IJ, Krooshoop DJ, Scharenborg NM, Lesterhuis WJ, Diepstra JH, Van Muijen GN, Strijk SP, Ruers TJ, Boerman OC, Oyen WJ, et al. 2003. Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res. 63(1):12–17.
  • Demoulin S, Herfs M, Delvenne P, Hubert P. 2013. Tumor microenvironment converts plasmacytoid dendritic cells into immunosuppressive/tolerogenic cells: insight into the molecular mechanisms. J Leukoc Biol. 93(3):343–52.
  • Dhodapkar MV, Sznol M, Zhao B, Wang D, Carvajal RD, Keohan ML, Chuang E, Sanborn RE, Lutzky J, Powderly J, et al. 2014. Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205. Sci Transl Med. 6(232):232ra51.
  • Di Nicola M, Carlo-Stella C, Mortarini R, Baldassari P, Guidetti A, Gallino GF, Del Vecchio M, Ravagnani F, Magni M, Chaplin P, et al. 2004. Boosting T cell-mediated immunity to tyrosinase by vaccinia virus-transduced, CD34(+)-derived dendritic cell vaccination: a phase I trial in metastatic melanoma. Clin Cancer Res. 10(16):5381–90.
  • Di Pucchio T, Chatterjee B, Smed-Sorensen A, Clayton S, Palazzo A, Montes M, Xue Y, Mellman I, Banchereau J, Connolly JE. 2008. Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I. Nat Immunol. 9(5):551–57.
  • Dress RJ, Dutertre CA, Giladi A, Schlitzer A, Low I, Shadan NB, Tay A, Lum J, Kairi M, Hwang YY, et al. 2019. Plasmacytoid dendritic cells develop from Ly6D(+) lymphoid progenitors distinct from the myeloid lineage. Nat Immunol. 20(7):852–64.
  • Drobits B, Holcmann M, Amberg N, Swiecki M, Grundtner R, Hammer M, Colonna M, Sibilia M. 2012. Imiquimod clears tumors in mice independent of adaptive immunity by converting pDcs into tumor-killing effector cells. J Clin Invest. 122(2):575–85.
  • Duong E, Fessenden TB, Lutz E, Dinter T, Yim L, Blatt S, Bhutkar A, Wittrup KD, Spranger S. 2021. Type I interferon activates MHC class I-dressed CD11b+ conventional dendritic cells to promote protective anti-tumor CD8+ T cell immunity. Immunity. 55(2):308–23.e9.
  • Dutertre CA, Becht E, Irac SE, Khalilnezhad A, Narang V, Khalilnezhad S, Ng PY, van den Hoogen LL, Leong JY, Lee B, et al. 2019. Single-cell analysis of human mononuclear phagocytes reveals subset-defining markers and identifies circulating inflammatory dendritic cells. Immunity. 51(3):573–89 e8.
  • Embgenbroich M, Burgdorf S. 2018. Current concepts of antigen cross-presentation. Front Immunol. 9:1643.
  • Escudier B, Dorval T, Chaput N, Andre F, Caby MP, Novault S, Flament C, Leboulaire C, Borg C, Amigorena S, et al. 2005. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. J Transl Med. 3(1):10.
  • Ferris ST, Durai V, Wu R, Theisen DJ, Ward JP, Bern MD, Jtt D, Bagadia P, Liu T, Briseno CG, et al. 2020. cDC1 prime and are licensed by CD4(+) T cells to induce anti-tumour immunity. Nature. 584(7822):624–29.
  • Fromm PD, Papadimitrious MS, Hsu JL, Van Kooten Losio N, Verma ND, Lo TH, Silveira PA, Bryant CE, Turtle CJ, Prue RL, et al. 2016. CMRF-56(+) blood dendritic cells loaded with mRNA induce effective antigen-specific cytotoxic T-lymphocyte responses. Oncoimmunology. 5(6):e1168555.
  • Fu C, Jiang A. 2018. Dendritic cells and CD8 T cell immunity in tumor microenvironment. Front Immunol. 9:3059.
  • Fu C, Liang X, Cui W, Ober-Blobaum JL, Vazzana J, Shrikant PA, Lee KP, Clausen BE, Mellman I, Jiang A. 2015. Beta-catenin in dendritic cells exerts opposite functions in cross-priming and maintenance of CD8+ T cells through regulation of IL-10. Proc Natl Acad Sci USA. 112(9):2823–28.
  • Fu C, Peng P, Loschko J, Feng L, Pham P, Cui W, Lee KP, Krug AB, Jiang A. 2020a. Plasmacytoid dendritic cells cross-prime naive CD8 T cells by transferring antigen to conventional dendritic cells through exosomes. Proc Natl Acad Sci USA. 117:23730–41.
  • Fu C, Zhou L, Mi QS, Jiang A. 2020b. DC-based vaccines for cancer immunotherapy. Vaccines (Basel). 8:4.
  • Fu C, Zhou L, Mi QS, Jiang A. 2022. Plasmacytoid dendritic cells and cancer immunotherapy. Cells. 11(2):222.
  • Fuertes MB, Woo SR, Burnett B, Fu YX, Gajewski TF. 2013. Type I interferon response and innate immune sensing of cancer. Trends Immunol. 34(2):67–73.
  • Gardner A, de Mingo Pulido A, Ruffell B. 2020. Dendritic cells and their role in immunotherapy. Front Immunol. 11:924.
  • Gargett T, Abbas MN, Rolan P, Price JD, Gosling KM, Ferrante A, Ruszkiewicz A, Atmosukarto IIC, Altin J, Parish CR, et al. 2018. Phase I trial of Lipovaxin-MM, a novel dendritic cell-targeted liposomal vaccine for malignant melanoma. Cancer Immunol Immunother. 67(9):1461–72.
  • GeurtsvanKessel CH, Willart MA, van Rijt LS, Muskens F, Kool M, Baas C, Thielemans K, Bennett C, Clausen BE, Hoogsteden HC, et al. 2008. Clearance of influenza virus from the lung depends on migratory langerin+cd11b- but not plasmacytoid dendritic cells. J Exp Med. 205(7):1621–34.
  • Ghosh HS, Cisse B, Bunin A, Lewis KL, Reizis B. 2010. Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity. 33(6):905–16.
  • Gilfillan CB, Kuhn S, Baey C, Hyde EJ, Yang J, Ruedl C, Ronchese F. 2018. Clec9a(+) dendritic cells are not essential for antitumor CD8(+) T cell responses induced by Poly I:C immunotherapy. J Immunol. 200(8):2978–86.
  • Goudot C, Coillard A, Villani AC, Gueguen P, Cros A, Sarkizova S, Tang-Huau TL, Bohec M, Baulande S, Hacohen N, et al. 2017. Aryl hydrocarbon receptor controls monocyte differentiation into dendritic cells versus macrophages. Immunity. 47(3):582–96 e6.
  • Grajkowska LT, Ceribelli M, Lau CM, Warren ME, Tiniakou I, Nakandakari Higa S, Bunin A, Haecker H, Mirny LA, Staudt LM, et al. 2017. Isoform-specific expression and feedback regulation of E protein TCF4 control dendritic cell lineage specification. Immunity. 46(1):65–77.
  • Granot T, Senda T, Carpenter DJ, Matsuoka N, Weiner J, Gordon CL, Miron M, Kumar BV, Griesemer A, Ho SH, et al. 2017. Dendritic cells display subset and tissue-specific maturation dynamics over human life. Immunity. 46(3):504–15.
  • Greter M, Helft J, Chow A, Hashimoto D, Mortha A, Agudo-Cantero J, Bogunovic M, Gautier EL, Miller J, Leboeuf M, et al. 2012. GM-CSF controls nonlymphoid tissue dendritic cell homeostasis but is dispensable for the differentiation of inflammatory dendritic cells. Immunity. 36(6):1031–46.
  • Guery L, Dubrot J, Lippens C, Brighouse D, Malinge P, Irla M, Pot C, Reith W, Waldburger JM, Hugues S. 2014. Ag-presenting CpG-activated pDcs prime Th17 cells that induce tumor regression. Cancer Res. 74(22):6430–40.
  • Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, Schraml BU, Segura E, Tussiwand R, Yona S. 2014. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol. 14(8):571–78.
  • Gutierrez-Martinez E, Planes R, Anselmi G, Reynolds M, Menezes S, Adiko AC, Saveanu L, Guermonprez P. 2015. Cross-presentation of cell-associated antigens by MHC class I in dendritic cell subsets. Front Immunol. 63:63.
  • Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, Ravetch JV, Steinman RM, Nussenzweig MC. 2001. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med. 194(6):769–80.
  • Heger L, Hofer TP, Bigley V, de Vries IJM, Dalod M, Dudziak D, Ziegler-Heitbrock L. 2020. Subsets of CD1c(+) DCs: dendritic cell versus monocyte lineage. Front Immunol. 11:559166.
  • Hemann EA, Sjaastad LE, Langlois RA, Legge KL. 2015. Plasmacytoid dendritic cells require direct infection to sustain the pulmonary influenza a virus-specific CD8 T cell response. J Virol. 90(6):2830–37.
  • Herman JS, Grun D. 2018. FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq data. Nat Methods. 15(5):379–86.
  • Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, Calderon B, Schraml BU, Unanue ER, Diamond MS, et al. 2008. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science. 322(5904):1097–100.
  • Hiltbrunner S, Larssen P, Eldh M, Martinez-Bravo MJ, Wagner AK, Karlsson MC, Gabrielsson S. 2016. Exosomal cancer immunotherapy is independent of MHC molecules on exosomes. Oncotarget. 7(25):38707–17.
  • Hoeffel G, Ripoche AC, Matheoud D, Nascimbeni M, Escriou N, Lebon P, Heshmati F, Guillet JG, Gannage M, Caillat-Zucman S, et al. 2007. Antigen crosspresentation by human plasmacytoid dendritic cells. Immunity. 27(3):481–92.
  • Hong Y, Manoharan I, Suryawanshi A, Majumdar T, Angus-Hill ML, Koni PA, Manicassamy B, Mellor AL, Munn DH, Manicassamy S. 2015. Beta-catenin promotes regulatory T-cell responses in tumors by inducing vitamin a metabolism in dendritic cells. Cancer Res. 75(4):656–65.
  • Hsu JL, Bryant CE, Papadimitrious MS, Kong B, Gasiorowski RE, Orellana D, McGuire HM, Groth BFS, Joshua DE, Ho PJ, et al. 2018. A blood dendritic cell vaccine for acute myeloid leukemia expands anti-tumor T cell responses at remission. Oncoimmunology. 7(4):e1419114.
  • Hu Z, Leet DE, Allesoe RL, Oliveira G, Li S, Luoma AM, Liu J, Forman J, Huang T, Iorgulescu JB, et al. 2021. Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma. Nat Med. 27(3):515–25.
  • Huang MN, Nicholson LT, Batich KA, Swartz AM, Kopin D, Wellford S, Prabhakar VK, Woroniecka K, Nair SK, Fecci PE, et al. 2020. Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses. J Clin Invest. 130(2):774–88.
  • Huber A, Dammeijer F, Aerts J, Vroman H. 2018. Current state of dendritic cell-based immunotherapy: opportunities for in vitro antigen loading of different DC subsets? Front Immunol. 9:2804.
  • Iwanowycz S, Ngoi S, Li Y, Hill M, Koivisto C, Parrish M, Guo B, Li Z, Liu B. 2021. Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors. JCI Insight. 6(17). doi:10.1172/jci.insight.145885
  • Jhunjhunwala S, Hammer C, Delamarre L. 2021. Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion. Nat Rev Cancer. 21(5):298–312.
  • Joffre OP, Segura E, Savina A, Amigorena S. 2012. Cross-presentation by dendritic cells. Nat Rev Immunol. 12(8):557–69.
  • Jongbloed SL, Kassianos AJ, McDonald KJ, Clark GJ, Ju X, Angel CE, Chen CJ, Dunbar PR, Wadley RB, Jeet V, et al. 2010. Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J Exp Med. 207(6):1247–60.
  • Kalb ML, Glaser A, Stary G, Koszik F, Stingl G. 2012. TRAIL(+) human plasmacytoid dendritic cells kill tumor cells in vitro: mechanisms of imiquimod- and IFN-alpha-mediated antitumor reactivity. J Immunol. 188(4):1583–91.
  • Kalluri R, LeBleu VS. 2020. The biology, function, and biomedical applications of exosomes. Science. 367(6478). doi:10.1126/science.aau6977
  • Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, et al. 2010. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 363(5):411–22.
  • Kaplan DH. 2017. Ontogeny and function of murine epidermal Langerhans cells. Nat Immunol. 18(10):1068–75.
  • Karsunky H, Merad M, Mende I, Manz MG, Engleman EG, Weissman IL. 2005. Developmental origin of interferon-alpha-producing dendritic cells from hematopoietic precursors. Exp Hematol. 33(2):173–81.
  • Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, Oliveira G, Giobbie-Hurder A, Felt K, Gjini E, et al. 2019. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 565(7738):234–39.
  • Kiessler M, Plesca I, Sommer U, Wehner R, Wilczkowski F, Muller L, Tunger A, Lai X, Rentsch A, Peuker K, et al. 2021. Tumor-Infiltrating plasmacytoid dendritic cells are associated with survival in human colon cancer. J Immunother Cancer. 9(3):e001813.
  • Klechevsky E, Flamar AL, Cao Y, Blanck JP, Liu M, O’Bar A, Agouna-Deciat O, Klucar P, Thompson-Snipes L, Zurawski S, et al. 2010. Cross-priming CD8+ T cells by targeting antigens to human dendritic cells through DCIR. Blood. 116(10):1685–97.
  • Kleindienst P, Brocker T. 2003. Endogenous dendritic cells are required for amplification of T cell responses induced by dendritic cell vaccines in vivo. J Immunol. 170(6):2817–23.
  • Koyama M, Hashimoto D, Aoyama K, Matsuoka K, Karube K, Niiro H, Harada M, Tanimoto M, Akashi K, Teshima T. 2009. Plasmacytoid dendritic cells prime alloreactive T cells to mediate graft-versus-host disease as antigen-presenting cells. Blood. 113(9):2088–95.
  • Kranz LM, Diken M, Haas H, Kreiter S, Loquai C, Reuter KC, Meng M, Fritz D, Vascotto F, Hefesha H, et al. 2016. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature. 534(7607):396–401.
  • Kumar J, Kale V, Limaye L. 2015. Umbilical cord blood-derived CD11c(+) dendritic cells could serve as an alternative allogeneic source of dendritic cells for cancer immunotherapy. Stem Cell Res Ther. 6:6184.
  • Kurts C, Robinson BW, Knolle PA. 2010. Cross-priming in health and disease. Nat Rev Immunol. 10(6):403–14.
  • Kvedaraite E, Ginhoux F. 2022. Human dendritic cells in cancer. Sci Immunol. 7(70):eabm9409.
  • Le Mercier I, Poujol D, Sanlaville A, Sisirak V, Gobert M, Durand I, Dubois B, Treilleux I, Marvel J, Vlach J, et al. 2013. Tumor promotion by intratumoral plasmacytoid dendritic cells is reversed by TLR7 ligand treatment. Cancer Res. 73(15):4629–40.
  • Lee HK, Zamora M, Linehan MM, Iijima N, Gonzalez D, Haberman A, Iwasaki A. 2009. Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection. J Exp Med. 206(2):359–70.
  • Lenogue K, Walencik A, Laulagnier K, Molens JP, Benlalam H, Dreno B, Coulie P, Pule M, Chaperot L, Plumas J. 2021. Engineering a human plasmacytoid dendritic cell-based vaccine to prime and expand multispecific viral and tumor antigen-specific T-cells. Vaccines (Basel). 9(2). doi:10.3390/vaccines9020141
  • Li S, Wu J, Zhu S, Liu YJ, Chen J. 2017. Disease-associated plasmacytoid dendritic cells. Front Immunol. 8:1268.
  • Liang X, Fu C, Cui W, Ober-Blobaum JL, Zahner SP, Shrikant PA, Clausen BE, Flavell RA, Mellman I, Jiang A. 2014. Beta-catenin mediates tumor-induced immunosuppression by inhibiting cross-priming of CD8(+) T cells. J Leukoc Biol. 95(1):179–90.
  • Liu C, Lou Y, Lizee G, Qin H, Liu S, Rabinovich B, Kim GJ, Wang YH, Ye Y, Sikora AG, et al. 2008. Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice. J Clin Invest. 118(3):1165–75.
  • Lombardi VC, Khaiboullina SF, Rizvanov AA. 2015. Plasmacytoid dendritic cells, a role in neoplastic prevention and progression. Eur J Clin Invest. 45 Suppl:1–8.
  • Lou Y, Liu C, Kim GJ, Liu YJ, Hwu P, Wang G. 2007. Plasmacytoid dendritic cells synergize with myeloid dendritic cells in the induction of antigen-specific antitumor immune responses. J Immunol. 178(3):1534–41.
  • Lozza L, Farinacci M, Fae K, Bechtle M, Staber M, Dorhoi A, Bauer M, Ganoza C, Weber S, Kaufmann SH. 2014. Crosstalk between human DC subsets promotes antibacterial activity and CD8+ T-cell stimulation in response to bacille Calmette-Guerin. Eur J Immunol. 44(1):80–92.
  • Lundberg K, Albrekt AS, Nelissen I, Santegoets S, de Gruijl TD, Gibbs S, Lindstedt M. 2013. Transcriptional profiling of human dendritic cell populations and models–unique profiles of in vitro dendritic cells and implications on functionality and applicability. PLoS One. 8(1):e52875.
  • Mackensen A, Herbst B, Chen JL, Kohler G, Noppen C, Herr W, Spagnoli GC, Cerundolo V, Lindemann A. 2000. Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. Int J Cancer. 86(3):385–92.
  • Macri C, Dumont C, Johnston AP, Mintern JD. 2016. Targeting dendritic cells: a promising strategy to improve vaccine effectiveness. Clin Transl Immunology. 5(3):e66.
  • Marciscano AE, Anandasabapathy N. 2021. The role of dendritic cells in cancer and anti-tumor immunity. Semin Immunol. 52:101481.
  • Marigo I, Zilio S, Desantis G, Mlecnik B, Agnellini AH, Ugel S, Sasso MS, Qualls JE, Kratochvill F, Zanovello P, et al. 2016. T cell cancer therapy requires CD40-CD40L activation of tumor necrosis factor and inducible nitric-oxide-synthase-producing dendritic cells. Cancer Cell. 30(4):651.
  • Mastelic-Gavillet B, Balint K, Boudousquie C, Gannon PO, Kandalaft LE. 2019. Personalized dendritic cell vaccines-recent breakthroughs and encouraging clinical results. Front Immunol. 10:766.
  • Mathieu M, Martin-Jaular L, Lavieu G, Thery C. 2019. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 21(1):9–17.
  • Matsui T, Connolly JE, Michnevitz M, Chaussabel D, Yu CI, Glaser C, Tindle S, Pypaert M, Freitas H, Piqueras B, et al. 2009. CD2 distinguishes two subsets of human plasmacytoid dendritic cells with distinct phenotype and functions. J Immunol. 182(11):6815–23.
  • Merad M, Sathe P, Helft J, Miller J, Mortha A. 2013. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 31:563–604.
  • Mitchell D, Chintala S, Dey M. 2018. Plasmacytoid dendritic cell in immunity and cancer. J Neuroimmunol. 322:63–73.
  • Mittag D, Proietto AI, Loudovaris T, Mannering SI, Vremec D, Shortman K, Wu L, Harrison LC. 2011. Human dendritic cell subsets from spleen and blood are similar in phenotype and function but modified by donor health status. J Immunol. 186(11):6207–17.
  • Mittal D, Vijayan D, Putz EM, Aguilera AR, Markey KA, Straube J, Kazakoff S, Nutt SL, Takeda K, Hill GR, et al. 2017. Interleukin-12 from CD103(+) Batf3-Dependent dendritic cells required for NK-cell suppression of metastasis. Cancer Immunol Res. 5(12):1098–108.
  • Moffat JM, Segura E, Khoury G, Caminschi I, Cameron PU, Lewin SR, Villadangos JA, Mintern JD. 2013. Targeting antigen to bone marrow stromal cell-2 expressed by conventional and plasmacytoid dendritic cells elicits efficient antigen presentation. Eur J Immunol. 43(3):595–605.
  • Mohamadzadeh M, Berard F, Essert G, Chalouni C, Pulendran B, Davoust J, Bridges G, Palucka AK, Banchereau J. 2001. Interleukin 15 skews monocyte differentiation into dendritic cells with features of Langerhans cells. J Exp Med. 194(7):1013–20.
  • Morse MA, Chapman R, Powderly J, Blackwell K, Keler T, Green J, Riggs R, He LZ, Ramakrishna V, Vitale L, et al. 2011. Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with toll-like receptor stimulation to induce immunity to self-antigens in cancer patients. Clin Cancer Res. 17(14):4844–53.
  • Morse MA, Coleman RE, Akabani G, Niehaus N, Coleman D, Lyerly HK. 1999. Migration of human dendritic cells after injection in patients with metastatic malignancies. Cancer Res. 59(1):56–58.
  • Morse MA, Garst J, Osada T, Khan S, Hobeika A, Clay TM, Valente N, Shreeniwas R, Sutton MA, Delcayre A, et al. 2005. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med. 3(1):9.
  • Mouries J, Moron G, Schlecht G, Escriou N, Dadaglio G, Leclerc C. 2008. Plasmacytoid dendritic cells efficiently cross-prime naive T cells in vivo after TLR activation. Blood. 112(9):3713–22.
  • Murphy TL, Murphy KM. 2022. Dendritic cells in cancer immunology. Cell Mol Immunol. 19(1):3–13.
  • Musumeci A, Lutz K, Winheim E, Krug AB. 2019. What makes a pDC: recent advances in understanding plasmacytoid DC development and heterogeneity. Front Immunol. 10:1222.
  • Nakayama M. 2014. Antigen presentation by MHC-dressed cells. Front Immunol. 5:672.
  • Naslund TI, Gehrmann U, Qazi KR, Karlsson MC, Gabrielsson S. 2013. Dendritic cell-derived exosomes need to activate both T and B cells to induce antitumor immunity. J Immunol. 190(6):2712–19.
  • Nierkens S, den Brok MH, Garcia Z, Togher S, Wagenaars J, Wassink M, Boon L, Ruers TJ, Figdor CG, Schoenberger SP, et al. 2011. Immune adjuvant efficacy of CpG oligonucleotide in cancer treatment is founded specifically upon TLR9 function in plasmacytoid dendritic cells. Cancer Res. 71(20):6428–37.
  • Nierkens S, Tel J, Janssen E, Adema GJ. 2013. Antigen cross-presentation by dendritic cell subsets: one general or all sergeants? Trends Immunol. 34(8):361–70.
  • Nizzoli G, Krietsch J, Weick A, Steinfelder S, Facciotti F, Gruarin P, Bianco A, Steckel B, Moro M, Crosti M, et al. 2013. Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses. Blood. 122(6):932–42.
  • Oberkampf M, Guillerey C, Mouries J, Rosenbaum P, Fayolle C, Bobard A, Savina A, Ogier-Denis E, Enninga J, Amigorena S, et al. 2018. Mitochondrial reactive oxygen species regulate the induction of CD8(+) T cells by plasmacytoid dendritic cells. Nat Commun. 9(1):2241.
  • Ott PA, Hu-Lieskovan S, Chmielowski B, Govindan R, Naing A, Bhardwaj N, Margolin K, Awad MM, Hellmann MD, Lin JJ, et al. 2020. A Phase Ib trial of personalized neoantigen therapy plus anti-PD-1 in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. Cell. 183(2):347–62 e24.
  • Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, Zhang W, Luoma A, Giobbie-Hurder A, Peter L, et al. 2017. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 547(7662):217–21.
  • Palucka K, Banchereau J. 2013. Dendritic-Cell-Based therapeutic cancer vaccines. Immunity. 39(1):38–48.
  • Pavlick A, Blazquez AB, Meseck M, Lattanzi M, Ott PA, Marron TU, Holman RM, Mandeli J, Salazar AM, McClain CB, et al. 2020. Combined vaccination with NY-ESO-1 protein, poly-ICLC, and montanide improves humoral and cellular immune responses in patients with high-risk melanoma. Cancer Immunol Res. 8(1):70–80.
  • Pelayo R, Hirose J, Huang J, Garrett KP, Delogu A, Busslinger M, Kincade PW. 2005. Derivation of 2 categories of plasmacytoid dendritic cells in murine bone marrow. Blood. 105(11):4407–15.
  • Petersen TR, Sika-Paotonu D, Knight DA, Simkins HM, Hermans IF. 2011. Exploiting the role of endogenous lymphoid-resident dendritic cells in the priming of NKT cells and CD8+ T cells to dendritic cell-based vaccines. PLoS One. 6(3):e17657.
  • Pitt JM, Andre F, Amigorena S, Soria JC, Eggermont A, Kroemer G, Zitvogel L. 2016. Dendritic cell-derived exosomes for cancer therapy. J Clin Invest. 126(4):1224–32.
  • Poropatich K, Dominguez D, Chan WC, Andrade J, Zha Y, Wray B, Miska J, Qin L, Cole L, Coates S, et al. 2020. OX40+ plasmacytoid dendritic cells in the tumor microenvironment promote antitumor immunity. J Clin Invest. 130(7):3528–42.
  • Poulin LF, Salio M, Griessinger E, Anjos-Afonso F, Craciun L, Chen JL, Keller AM, Joffre O, Zelenay S, Nye E, et al. 2010. Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells. J Exp Med. 207(6):1261–71.
  • Prue RL, Vari F, Radford KJ, Tong H, Hardy MY, D’Rozario R, Waterhouse NJ, Rossetti T, Coleman R, Tracey C, et al. 2015. A phase I clinical trial of CD1c (BDCA-1)+ dendritic cells pulsed with HLA-A*0201 peptides for immunotherapy of metastatic hormone refractory prostate cancer. J Immunother (1991). 38(2):71–76.
  • Ratzinger G, Baggers J, de Cos MA, Yuan J, Dao T, Reagan JL, Munz C, Heller G, Young JW. 2004. Mature human Langerhans cells derived from CD34+ hematopoietic progenitors stimulate greater cytolytic T lymphocyte activity in the absence of bioactive IL-12p70, by either single peptide presentation or cross-priming, than do dermal-interstitial or monocyte-derived dendritic cells. J Immunol. 173(4):2780–91.
  • Reardon DA, Mitchell DA. 2017. The development of dendritic cell vaccine-based immunotherapies for glioblastoma. Semin Immunopathol. 39(2):225–39.
  • Reizis B, Colonna M, Trinchieri G, Barrat F, Gilliet M. 2011. Plasmacytoid dendritic cells: one-trick ponies or workhorses of the immune system? Nat Rev Immunol. 11(8):558–65.
  • Rodrigues PF, Alberti-Servera L, Eremin A, Grajales-Reyes GE, Ivanek R, Tussiwand R. 2018. Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells. Nat Immunol. 19(7):711–22.
  • Rogers GL, Shirley JL, Zolotukhin I, Kumar SRP, Sherman A, Perrin GQ, Hoffman BE, Srivastava A, Basner-Tschakarjan E, Wallet MA, et al. 2017. Plasmacytoid and conventional dendritic cells cooperate in crosspriming AAV capsid-specific CD8(+) T cells. Blood. 129(24):3184–95.
  • Roudko V, Greenbaum B, Bhardwaj N 2020. Computational prediction and validation of tumor-associated neoantigens. Front Immunol. 1127.
  • Ruhland MK, Roberts EW, Cai E, Mujal AM, Marchuk K, Beppler C, Nam D, Serwas NK, Binnewies M, Krummel MF. 2020. Visualizing synaptic transfer of tumor antigens among dendritic cells. Cancer Cell. 37(6):786–99 e5.
  • Salio M, Palmowski MJ, Atzberger A, Hermans IF, Cerundolo V. 2004. CpG-matured murine plasmacytoid dendritic cells are capable of in vivo priming of functional CD8 T cell responses to endogenous but not exogenous antigens. J Exp Med. 199(4):567–79.
  • Salmon H, Idoyaga J, Rahman A, Leboeuf M, Remark R, Jordan S, Casanova-Acebes M, Khudoynazarova M, Agudo J, Tung N, et al. 2016. Expansion and activation of CD103(+) dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition. Immunity. 44(4):924–38.
  • Samuel M, Gabrielsson S. 2019. Personalized medicine and back-allogeneic exosomes for cancer immunotherapy. J Intern Med. 289:138–46.
  • Sanchez-Paulete AR, Cueto FJ, Martinez-Lopez M, Labiano S, Morales-Kastresana A, Rodriguez-Ruiz ME, Jure-Kunkel M, Azpilikueta A, Aznar MA, Quetglas JI, et al. 2016. Cancer immunotherapy with immunomodulatory anti-CD137 and anti-PD-1 monoclonal antibodies requires BATF3-dependent dendritic cells. Cancer Discov. 6(1):71–79.
  • Sanchez-Paulete AR, Teijeira A, Cueto FJ, Garasa S, Perez-Gracia JL, Sanchez-Arraez A, Sancho D, Melero I. 2017. Antigen cross-presentation and T-cell cross-priming in cancer immunology and immunotherapy. Ann Oncol. 28(suppl_12):xii44–xii55.
  • Santos PM, Butterfield LH. 2018. Dendritic cell-based cancer vaccines. J Immunol. 200(2):443–49.
  • Sapoznikov A, Fischer JA, Zaft T, Krauthgamer R, Dzionek A, Jung S. 2007. Organ-dependent in vivo priming of naive CD4+, but not CD8+, T cells by plasmacytoid dendritic cells. J Exp Med. 204(8):1923–33.
  • Sathe P, Vremec D, Wu L, Corcoran L, Shortman K. 2013. Convergent differentiation: myeloid and lymphoid pathways to murine plasmacytoid dendritic cells. Blood. 121(1):11–19.
  • Saxena M, Bhardwaj N. 2018. Re-emergence of dendritic cell vaccines for cancer treatment. Trends in Cancer. 4(2):119–37.
  • Schreibelt G, Bol KF, Westdorp H, Wimmers F, Aarntzen EH, Duiveman-de Boer T, van de Rakt MW, Scharenborg NM, de Boer AJ, Pots JM, et al. 2016. Effective clinical responses in metastatic melanoma patients after vaccination with primary myeloid dendritic cells. Clin Cancer Res. 22(9):2155–66.
  • See P, Dutertre CA, Chen J, Gunther P, McGovern N, Irac SE, Gunawan M, Beyer M, Handler K, Duan K, et al. 2017. Mapping the human DC lineage through the integration of high-dimensional techniques. Science. 356(6342). doi:10.1126/science.aag3009.
  • Segura E. 2022. Human dendritic cell subsets: an updated view of their ontogeny and functional specialization. Eur J Immunol. doi:10.1002/eji.202149632
  • Segura E, Durand M, Amigorena S. 2013. Similar antigen cross-presentation capacity and phagocytic functions in all freshly isolated human lymphoid organ-resident dendritic cells. J Exp Med. 210(5):1035–47.
  • Sehgal K, Dhodapkar KM, Dhodapkar MV. 2014. Targeting human dendritic cells in situ to improve vaccines. Immunol Lett. 162(1 Pt A):59–67.
  • Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH. 2007. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J Clin Invest. 117(9):2570–82.
  • Shigematsu H, Reizis B, Iwasaki H, Mizuno S, Hu D, Traver D, Leder P, Sakaguchi N, Akashi K. 2004. Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin. Immunity. 21(1):43–53.
  • Shinde P, Fernandes S, Melinkeri S, Kale V, Limaye L. 2018. Compromised functionality of monocyte-derived dendritic cells in multiple myeloma patients may limit their use in cancer immunotherapy. Sci Rep. 8(1):5705.
  • Sichien D, Scott CL, Martens L, Vanderkerken M, Van Gassen S, Plantinga M, Joeris T, De Prijck S, Vanhoutte L, Vanheerswynghels M, et al. 2016. IRF8 Transcription factor controls survival and function of terminally differentiated conventional and plasmacytoid dendritic cells, respectively. Immunity. 45(3):626–40.
  • Silk KM, Silk JD, Ichiryu N, Davies TJ, Nolan KF, Leishman AJ, Carpenter L, Watt SM, Cerundolo V, Fairchild PJ. 2012. Cross-presentation of tumour antigens by human induced pluripotent stem cell-derived CD141(+)XCR1+ dendritic cells. Gene Ther. 19(10):1035–40.
  • Somaiah N, Block MS, Kim JW, Shapiro GI, Do KT, Hwu P, Eder JP, Jones RL, Lu H, Ter Meulen JH, et al. 2019. First-in-class, first-in-human study evaluating LV305, a dendritic-cell tropic lentiviral vector, in sarcoma and other solid tumors expressing NY-ESO-1. Clin Cancer Res. 25(19):5808–17.
  • Spranger S, Bao R, Gajewski TF. 2015. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature. 523(7559):231–35.
  • Spranger S, Dai D, Horton B, Gajewski TF. 2017. Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell. 31(5):711–23 e4.
  • Stary G, Bangert C, Tauber M, Strohal R, Kopp T, Stingl G. 2007. Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells. J Exp Med. 204(6):1441–51.
  • Steinman RM. 2012. Decisions about dendritic cells: past, present, and future. Annu Rev Immunol. 30:1–22.
  • Steinman RM, Banchereau J. 2007. Taking dendritic cells into medicine. Nature. 449(7161):419–26.
  • Steinman RM, Cohn ZA. 1973. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med. 137(5):1142–62.
  • Stoitzner P, Romani N, Rademacher C, Probst HC, Mahnke K. 2022. Antigen targeting to dendritic cells: still a place in future immunotherapy? Eur J Immunol. doi:10.1002/eji.202149515
  • Swiecki M, Colonna M. 2015. The multifaceted biology of plasmacytoid dendritic cells. Nat Rev Immunol. 15(8):471–85.
  • Takagi H, Fukaya T, Eizumi K, Sato Y, Sato K, Shibazaki A, Otsuka H, Hijikata A, Watanabe T, Ohara O, et al. 2011. Plasmacytoid dendritic cells are crucial for the initiation of inflammation and T cell immunity in vivo. Immunity. 35(6):958–71.
  • Tel J, Aarntzen EH, Baba T, Schreibelt G, Schulte BM, Benitez-Ribas D, Boerman OC, Croockewit S, Oyen WJ, van Rossum M, et al. 2013. Natural human plasmacytoid dendritic cells induce antigen-specific T-cell responses in melanoma patients. Cancer Res. 73(3):1063–75.
  • Theisen DJ, Davidson JT, Briseno CG, Gargaro M, Lauron EJ, Wang Q, Desai P, Durai V, Bagadia P, Brickner JR, et al. 2018. WDFY4 is required for cross-presentation in response to viral and tumor antigens. Science. 362(6415):694–99.
  • Theisen DJ, Ferris ST, Briseno CG, Kretzer N, Iwata A, Murphy KM, Murphy TL. 2019. Batf3-dependent genes control tumor rejection induced by dendritic cells independently of cross-presentation. Cancer Immunol Res. 7(1):29–39.
  • Thomas M, Ponce-Aix S, Navarro A, Riera-Knorrenschild J, Schmidt M, Wiegert E, Kapp K, Wittig B, Mauri C, Domine Gomez M, et al. 2018. Immunotherapeutic maintenance treatment with toll-like receptor 9 agonist lefitolimod in patients with extensive-stage small-cell lung cancer: results from the exploratory, controlled, randomized, international phase II IMPULSE study. Ann Oncol. 29(10):2076–84.
  • Thordardottir S, Hangalapura BN, Hutten T, Cossu M, Spanholtz J, Schaap N, Radstake TR, van der Voort R, Dolstra H. 2014. The aryl hydrocarbon receptor antagonist StemRegenin 1 promotes human plasmacytoid and myeloid dendritic cell development from CD34+ hematopoietic progenitor cells. Stem Cells Dev. 23(9):955–67.
  • Tian H, Li W. 2017. Dendritic cell-derived exosomes for cancer immunotherapy: hope and challenges. Ann Transl Med. 5(10):221.
  • Tran Janco JM, Lamichhane P, Karyampudi L, Knutson KL. 2015. Tumor-infiltrating dendritic cells in cancer pathogenesis. J Immunol. 194(7):2985–91.
  • Trumpfheller C, Longhi MP, Caskey M, Idoyaga J, Bozzacco L, Keler T, Schlesinger SJ, Steinman RM. 2012. Dendritic cell-targeted protein vaccines: a novel approach to induce T-cell immunity. J Intern Med. 271(2):183–92.
  • Tussiwand R, Everts B, Grajales-Reyes GE, Kretzer NM, Iwata A, Bagaitkar J, Wu X, Wong R, Anderson DA, Murphy TL, et al. 2015. Klf4 expression in conventional dendritic cells is required for T helper 2 cell responses. Immunity. 42(5):916–28.
  • van Willigen WW, Bloemendal M, Gerritsen WR, Schreibelt G, de Vries IJM, Bol KF. 2018. Dendritic cell cancer therapy: vaccinating the right patient at the right time. Front Immunol. 9:2265.
  • Veglia F, Gabrilovich DI. 2017. Dendritic cells in cancer: the role revisited. Curr Opin Immunol. 45:43–51.
  • Verheye E, Bravo Melgar J, Deschoemaeker S, Raes G, Maes A, De Bruyne E, Menu E, Vanderkerken K, Laoui D, De Veirman K. 2022. Dendritic cell-based immunotherapy in multiple myeloma: challenges, opportunities, and future directions. Int J Mol Sci. 23(2):904.
  • Verneau J, Sautes-Fridman C, Sun CM. 2020. Dendritic cells in the tumor microenvironment: prognostic and theranostic impact. Semin Immunol. 48:101410.
  • Villani AC, Satija R, Reynolds G, Sarkizova S, Shekhar K, Fletcher J, Griesbeck M, Butler A, Zheng S, Lazo S, et al. 2017. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science. 356(6335). doi:10.1126/science.aah4573.
  • Wakim LM, Bevan MJ. 2011. Cross-Dressed dendritic cells drive memory CD8+ T-cell activation after viral infection. Nature. 471(7340):629–32.
  • Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D. 2020. Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 20(1):7–24.
  • Westdorp H, Creemers JHA, van Oort IM, Schreibelt G, Gorris MAJ, Mehra N, Simons M, de Goede AL, van Rossum MM, Croockewit AJ, et al. 2019. Blood-derived dendritic cell vaccinations induce immune responses that correlate with clinical outcome in patients with chemo-naive castration-resistant prostate cancer. J Immunother Cancer. 7(1):302.
  • Wimmers F, Schreibelt G, Skold AE, Figdor CG, De Vries IJ. 2014. Paradigm shift in dendritic cell-based immunotherapy: from in vitro generated monocyte-derived DCs to naturally circulating DC subsets. Front Immunol. 5:165.
  • Yang GX, Lian ZX, Kikuchi K, Moritoki Y, Ansari AA, Liu YJ, Ikehara S, Gershwin ME. 2005. Plasmacytoid dendritic cells of different origins have distinct characteristics and function: studies of lymphoid progenitors versus myeloid progenitors. J Immunol. 175(11):7281–87.
  • Yao Y, Fu C, Zhou L, Mi QS, Jiang A. 2021. DC-derived exosomes for cancer immunotherapy. Cancers (Basel). 13(15):3667.
  • Ye Y, Gaugler B, Mohty M, Malard F. 2020. Plasmacytoid dendritic cell biology and its role in immune-mediated diseases. Clin Transl Immunol. 9(5):e1139.
  • Yewdall AW, Drutman SB, Jinwala F, Bahjat KS, Bhardwaj N. 2010. CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells. PLoS One. 5(6):e11144.
  • Yin X, Chen S, Eisenbarth SC. 2021. Dendritic cell regulation of T helper cells. Annu Rev Immunol. 397:59–90.
  • Yoneyama H, Matsuno K, Toda E, Nishiwaki T, Matsuo N, Nakano A, Narumi S, Lu B, Gerard C, Ishikawa S, et al. 2005. Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs. J Exp Med. 202(3):425–35.
  • Zhang H, Gregorio JD, Iwahori T, Zhang X, Choi O, Tolentino LL, Prestwood T, Carmi Y, Engleman EG. 2017. A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes. Proc Natl Acad Sci USA. 114(8):1988–93.
  • Zhang Y, Song J, Zhao Z, Yang M, Chen M, Liu C, Ji J, Zhu D. 2020. Single-cell transcriptome analysis reveals tumor immune microenvironment heterogenicity and granulocytes enrichment in colorectal cancer liver metastases. Cancer Lett. 470:84–94.
  • Zilionis R, Engblom C, Pfirschke C, Savova V, Zemmour D, Saatcioglu HD, Krishnan I, Maroni G, Meyerovitz CV, Kerwin CM, et al. 2019. Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species. Immunity. 50(5):1317–34 e10.

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