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Review

Conventional type 1 dendritic cells (cDC1) as cancer therapeutics: challenges and opportunities

ORCID Icon, ORCID Icon & ORCID Icon
Pages 465-472 | Received 23 Jul 2021, Accepted 14 Oct 2021, Published online: 26 Oct 2021

References

  • Saxena M, Van Der Burg SH, Melief CJM, et al. Therapeutic cancer vaccines. Nat Rev Cancer. 2021 Jun;21(6):360–378. PubMed PMID: 33907315.
  • O’Keeffe M, Mok WH, Radford KJ. Human dendritic cell subsets and function in health and disease. Cell Mol Life Sci. 2015 Nov;72(22):4309–4325. PubMed PMID: 26243730.
  • Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013 Jul 25;39(1):1–10. PubMed PMID: 23890059.
  • Garg AD, Coulie PG, Van den Eynde BJ, et al. Integrating next-generation dendritic cell vaccines into the current cancer immunotherapy landscape. Trends Immunol. 2017 Aug;38(8):577–593. PubMed PMID: 28610825.
  • Radford KJ, Tullett KM, Lahoud MH. Dendritic cells and cancer immunotherapy. Curr Opin Immunol. 2014 Apr;27:26–32. PubMed PMID: 24513968.
  • Wculek SK, Cueto FJ, Mujal AM, et al. Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2020 Jan;20(1):7–24. PubMed PMID: 31467405.
  • Lee YS, Radford KJ. The role of dendritic cells in cancer. Int Rev Cell Mol Biol. 2019;348:123–178. PubMed PMID: 31810552.
  • Cancel JC, Crozat K, Dalod M, et al. Are conventional type 1 dendritic cells critical for protective antitumor immunity and how? Front Immunol. 2019;10:9. PubMed PMID: 30809220; PubMed Central PMCID: PMC6379659.
  • Broz ML, Binnewies M, Boldajipour B, et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell. 2014 Nov 10;26(5):638–652. PubMed PMID: 25446897; PubMed Central PMCID: PMC4254577.
  • Spranger S, Dai D, Horton B, et al. Tumor-residing batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell. 2017 May 08;31(5):711–723e4. PubMed PMID: 28486109.
  • Barry KC, Hsu J, Broz ML, et al. A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments. Nat Med. 2018 Aug;24(8):1178–1191. PubMed PMID: 29942093.
  • Bottcher JP, Bonavita E, Chakravarty P, et al. NK cells stimulate recruitment of CDC1 into the tumor microenvironment promoting cancer immune control. Cell. 2018 Feb 22;172(5):1022–1037e14. PubMed PMID: 29429633; PubMed Central PMCID: PMC5847168.
  • Bol KF, Schreibelt G, Rabold K, et al. The clinical application of cancer immunotherapy based on naturally circulating dendritic cells. J Immunother Cancer. 2019 Apr 18;7(1):109. PubMed PMID: 30999964; PubMed Central PMCID: PMCPMC6471787.
  • Zhou Y, Slone N, Chrisikos TT, et al. Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103(+) conventional dendritic cells. J Immunother Cancer. 2020 Apr;8(1):e000474. PubMed PMID: 32273347; PubMed Central PMCID: PMCPMC7254126.
  • Lee YS, O’Brien LJ, Walpole CM, et al. Human CD141(+) dendritic cells (cDC1) are impaired in patients with advanced melanoma but can be targeted to enhance anti-PD-1 in a humanized mouse model. J Immunother Cancer. 2021 Mar;9(3):e001963. PubMed PMID: 33737342; PubMed Central PMCID: PMCPMC7978242.
  • Collin M, Bigley V. Human dendritic cell subsets: an update. Immunology. 2018 May;154(1):3–20. PubMed PMID: 29313948; PubMed Central PMCID: PMCPMC5904714.
  • Breton G, Lee J, Zhou YJ, et al. Circulating precursors of human CD1c+ and CD141+ dendritic cells. J Exp Med. 2015 Mar 9;212(3):401–413. PubMed PMID: 25687281; PubMed Central PMCID: PMC4354370.
  • Liu K, Nussenzweig MC. Origin and development of dendritic cells. Immunol Rev. 2010 Mar;234(1):45–54. PubMed PMID: 20193011.
  • Caux C, Vanbervliet B, Massacrier C, et al. CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha. J Exp Med. 1996 Aug 1;184(2):695–706. PubMed PMID: 8760823; PubMed Central PMCID: PMCPMC2192705.
  • Guo X, Zhou Y, Wu T, et al. Generation of mouse and human dendritic cells in vitro. J Immunol Methods. 2016 May;432:24–29. PubMed PMID: 26876301.
  • Poulin LF, Salio M, Griessinger E, et al. Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells. J Exp Med. 2010 Jun 7;207(6):1261–1271. PubMed PMID: 20479117; PubMed Central PMCID: PMC2882845.
  • Balan S, Ollion V, Colletti N, et al. 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 Iimmunol. 2014 Aug 15;193(4):1622–1635. PubMed PMID: 25009205; PubMed Central PMCID: PMC4120898.
  • Dontje W, Schotte R, Cupedo T, et al. Delta-like1-induced Notch1 signaling regulates the human plasmacytoid dendritic cell versus T-cell lineage decision through control of GATA-3 and Spi-B. Blood. 2006;107(6):2446–2452.
  • Olivier A, Lauret E, Gonin P, et al. The Notch ligand delta-1 is a hematopoietic development cofactor for plasmacytoid dendritic cells. Blood. 2006;107(7):2694–2701.
  • Demoulin S, Roncarati P, Delvenne P, et al. Production of large numbers of plasmacytoid dendritic cells with functional activities from CD34+ hematopoietic progenitor cells: use of interleukin-3. Exp Hematol. 2012;40(4):268–278.
  • Balan S, Arnold-Schrauf C, Abbas A, et al. Large-scale human dendritic cell differentiation revealing notch-dependent lineage Bifurcation and Heterogeneity. Cell Rep. 2018 Aug 14;24(7):1902–1915e6. PubMed PMID: 30110645; PubMed Central PMCID: PMC6113934.
  • Kirkling ME, Cytlak U, Lau CM, et al. Notch signaling facilitates in vitro generation of cross-presenting classical dendritic cells. Cell Rep. 2018 Jun 19;23(12):3658–3672e6. PubMed PMID: 29925006; PubMed Central PMCID: PMC6063084.
  • Proietto AI, Mittag D, Roberts AW, et al. The equivalents of human blood and spleen dendritic cell subtypes can be generated in vitro from human CD34(+) stem cells in the presence of fms-like tyrosine kinase 3 ligand and thrombopoietin. Cell Mol Immunol. 2012 Nov;9(6):446–454. PubMed PMID: 23085949; PubMed Central PMCID: PMCPMC4002222.
  • Lee J, Breton G, Oliveira TY, et al. Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow. J Exp Med. 2015 Mar 9;212(3):385–399. PubMed PMID: 25687283; PubMed Central PMCID: PMCPMC4354373.
  • Prue RL, Vari F, Radford KJ, et al. 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. 2015 Feb-Mar;38(2):71–76. PubMed PMID: 25658616.
  • Schreibelt G, Bol KF, Westdorp H, et al. Effective clinical responses in metastatic melanoma patients after vaccination with primary myeloid dendritic cells. Clin Cancer Res off J Am Assoc Cancer Res. 2016 May 1;22(9):2155–2166. PubMed PMID: 26712687.
  • Brewitz A, Eickhoff S, Dahling S, et al. CD8(+) T cells Orchestrate pDC-XCR1(+) dendritic cell spatial and functional cooperativity to optimize priming. Immunity. 2017 Feb 21;46(2):205–219. PubMed PMID: 28190711; PubMed Central PMCID: PMC5362251.
  • Lou Y, Liu C, Kim GJ, et al. Plasmacytoid dendritic cells synergize with myeloid dendritic cells in the induction of antigen-specific antitumor immune responses. J Iimmunol. 2007 Feb 1; 178(3)1534–1541. PubMed PMID: 17237402.
  • Eickhoff S, Brewitz A, Gerner MY, et al. Robust anti-viral immunity requires multiple distinct T cell-dendritic cell interactions. Cell. 2015 Sep 10;162(6):1322–1337. PubMed PMID: 26296422; PubMed Central PMCID: PMC4567961.
  • Ferris ST, Durai V, Wu R, et al. cDC1 prime and are licensed by CD4(+) T cells to induce anti-tumour immunity. Nature. 2020 Aug;584(7822):624–629. PubMed PMID: 32788723; PubMed Central PMCID: PMCPMC7469755.
  • Boitano AE, Wang J, Romeo R, et al. Aryl hydrocarbon receptor antagonists promote the expansion of human Hematopoietic stem cells. Science. 2010;329(5997):1345–1348.
  • Thordardottir S, Hangalapura BN, Hutten T, et al. The aryl hydrocarbon receptor antagonist StemRegenin 1 promotes human plasmacytoid and myeloid dendritic cell development from CD34+ hematopoietic progenitor cells. Stem Cells Dev. 2014 May 1;23(9):955–967. PubMed PMID: 24325394.
  • van Eck van der Sluijs J, Van Ens D, Thordardottir S, et al. Clinically applicable CD34(+)-derived blood dendritic cell subsets exhibit key subset-specific features and potently boost anti-tumor T and NK cell responses. Cancer Immunol Immunother. 2021 Apr 1. DOI:https://doi.org/10.1007/s00262-021-02899-3. PubMed PMID: 33796917.
  • Balan S, Kale VP, Limaye LS. A large number of mature and functional dendritic cells can be efficiently generated from umbilical cord blood-derived mononuclear cells by a simple two-step culture method. Transfusion. 2010 Nov;50(11):2413–2423. PubMed PMID: 20497510.
  • Kindwall-Keller TL, Ballen KK. Umbilical cord blood: the promise and the uncertainty. Stem Cells Transl Med. 2020 Oct;9(10):1153–1162. PubMed PMID: 32619330; PubMed Central PMCID: PMCPMC7519764.
  • Strong A, Gracner T, Chen P, et al. On the value of the umbilical cord blood supply. Value Health. 2018 Sep;21(9):1077–1082. PubMed PMID: 30224112.
  • WMDA global trends report 2020. 2021. Available from:https://wmda.info/wp-content/uploads/2021/05/GTR-2020-Summary-slides.pdf
  • De Gruijl TD, Van Den Eertwegh AJ, Pinedo HM, et al. Whole-cell cancer vaccination: from autologous to allogeneic tumor- and dendritic cell-based vaccines. Cancer Immunol Immunother. 2008 Oct;57(10):1569–1577. PubMed PMID: 18523771; PubMed Central PMCID: PMCPMC2491427.
  • Fabre JW. The allogeneic response and tumor immunity. Nat Med. 2001 Jun;7(6):649–652. PubMed PMID: 11385492.
  • Wang C, Li Z, Zhu Z, et al. Allogeneic dendritic cells induce potent antitumor immunity by activating KLRG1(+)CD8 T cells. Sci Rep. 2019 Oct 29;9(1):15527. PubMed PMID: 31664180; PubMed Central PMCID: PMCPMC6820535.
  • Trefzer U, Herberth G, Wohlan K, et al. Vaccination with hybrids of tumor and dendritic cells induces tumor-specific T-cell and clinical responses in melanoma stage III and IV patients. Int J Cancer. 2004 Jul 10;110(5):730–740. PubMed PMID: 15146563.
  • Tamir A, Basagila E, Kagahzian A, et al. Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors. Cancer Immunol Immunother. 2007 Dec;56(12):2003–2016. PubMed PMID: 17333181.
  • van de Loosdrecht AA, van Wetering S, Santegoets S, et al. A novel allogeneic off-the-shelf dendritic cell vaccine for post-remission treatment of elderly patients with acute myeloid leukemia. Cancer Immunol Immunother. 2018 Oct;67(10):1505–1518. PubMed PMID: 30039426; PubMed Central PMCID: PMCPMC6182404.
  • Laurell A, Lonnemark M, Brekkan E, et al. Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma. J Immunother Cancer. 2017;5(1):52. PubMed PMID: 28642820; PubMed Central PMCID: PMCPMC5477104.
  • Merad M, Manz MG. Dendritic cell homeostasis. Blood. 2009 Apr 9;113(15):3418–3427. PubMed PMID: 19176316; PubMed Central PMCID: PMCPMC2668851.
  • Sachamitr P, Leishman AJ, Davies TJ, et al. Directed differentiation of human induced pluripotent stem cells into dendritic cells displaying tolerogenic properties and resembling the CD141(+) subset. Front Immunol. 2017;8:1935. PubMed PMID: 29358940; PubMed Central PMCID: PMCPMC5766641.
  • Silk KM, Silk JD, Ichiryu N, et al. Cross-presentation of tumour antigens by human induced pluripotent stem cell-derived CD141(+)XCR1+ dendritic cells. Gene Ther. 2012 Oct;19(10):1035–1040. PubMed PMID: 22071967.
  • Sontag S, Forster M, Qin J, et al. Modelling IRF8 deficient human Hematopoiesis and dendritic cell development with engineered iPS cells. Stem Cells. 2017 Apr;35(4):898–908. PubMed PMID: 28090699.
  • Lee AS, Tang C, Rao MS, et al. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat Med. 2013 Aug;19(8):998–1004. PubMed PMID: 23921754; PubMed Central PMCID: PMCPMC3967018.
  • Hong SG, Dunbar CE, Winkler T. Assessing the risks of genotoxicity in the therapeutic development of induced pluripotent stem cells. Mol Ther. 2013 Feb;21(2):272–281. PubMed PMID: 23207694; PubMed Central PMCID: PMCPMC3594024.
  • Wculek SK, Amores-Iniesta J, Conde-Garrosa R, et al. Effective cancer immunotherapy by natural mouse conventional type-1 dendritic cells bearing dead tumor antigen. J Immunother Cancer. 2019 Apr 8;7(1):100. PubMed PMID: 30961656; PubMed Central PMCID: PMCPMC6454603.
  • Balam S, Kesselring R, Eggenhofer E, et al. Cross-presentation of dead-cell-associated antigens by DNGR-1(+) dendritic cells contributes to chronic allograft rejection in mice. Eur J Immunol. 2020 Dec;50(12):2041–2054. PubMed PMID: 32640051.
  • Kline DE, MacNabb BW, Chen X, et al. CD8alpha(+) dendritic cells dictate leukemia-specific CD8(+) T cell fates. J Iimmunol. 2018 Dec 15;201(12):3759–3769. PubMed PMID: 30420437; PubMed Central PMCID: PMCPMC6444187.
  • Ashour D, Arampatzi P, Pavlovic V, et al. IL-12 from endogenous cDC1, and not vaccine DC, is required for Th1 induction. JCI Insight. 2020 May 21;5(10). DOI:https://doi.org/10.1172/jci.insight.135143. PubMed PMID: 32434994; PubMed Central PMCID: PMCPMC7259537.
  • Yewdall AW, Drutman SB, Jinwala F, et al. CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells. PloS One. 2010 Jun 16;5(6):e11144. PubMed PMID: 20585396; PubMed Central PMCID: PMCPMC2886840.
  • Ruhland MK, Roberts EW, Cai E, et al. Visualizing synaptic transfer of tumor antigens among dendritic cells. Cancer Cell. 2020 Jun 8;37(6):786–799 e5. PubMed PMID: 32516589; PubMed Central PMCID: PMCPMC7671443.
  • Cueto FJ, Sancho D. The Flt3L/Flt3 axis in dendritic cell biology and cancer immunotherapy. Cancers (Basel). 2021 Mar 26;13(7):1525. PubMed PMID: 33810248; PubMed Central PMCID: PMCPMC8037622.
  • Hammerich L, Marron TU, Upadhyay R, et al. Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination. Nat Med. 2019 May;25(5):814–824. PubMed PMID: 30962585.
  • Oba T, Long MD, Keler T, et al. Overcoming primary and acquired resistance to anti-PD-L1 therapy by induction and activation of tumor-residing cDC1s. Nat Commun. 2020 Oct 27;11(1):5415. PubMed PMID: 33110069; PubMed Central PMCID: PMCPMC7592056.
  • Bhardwaj N, Friedlander PA, Pavlick AC, et al. Flt3 ligand augments immune responses to anti-DEC-205-NY-ESO-1 vaccine through expansion of dendritic cell subsets. Nat Cancer. 2020 2020 December 01;1(12):1204–1217.
  • Masterman KA, Haigh OL, Tullett KM, et al. Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141(+) dendritic cells to activate naive and memory NY-ESO-1-specific CD8(+) T cells. J Immunother Cancer. 2020 Jul;8(2). DOI:https://doi.org/10.1136/jitc-2020-000691. PubMed PMID: 32737142; PubMed Central PMCID: PMCPMC7394304.
  • Pearson FE, Tullett KM, Leal-Rojas IM, et al. Human CLEC9A antibodies deliver Wilms’ tumor 1 (WT1) antigen to CD141(+) dendritic cells to activate naive and memory WT1-specific CD8(+) T cells. Clin Transl Immunology. 2020;9(6):e1141. PubMed PMID: 32547743; PubMed Central PMCID: PMCPMC7292901.
  • Lahoud MH, Radford KJ. Enhancing the immunogenicity of cancer vaccines by harnessing CLEC9A. Hum Vaccin Immunother. 2021 Feb 24;1–5. DOI:https://doi.org/10.1080/21645515.2021.1873056. PubMed PMID: 33625943.
  • Mizumoto Y, Hemmi H, Katsuda M, et al. Anticancer effects of chemokine-directed antigen delivery to a cross-presenting dendritic cell subset with immune checkpoint blockade. Br J Cancer. 2020 Apr;122(8):1185–1193. PubMed PMID: 32066911; PubMed Central PMCID: PMCPMC7156711.

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