SpringerLink
Log in

Phenotypes and Functions of Human Dendritic Cell Subsets in the Tumor Microenvironment

  • Protocol
  • First Online:
Dendritic Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2618))

Abstract

Dendritic cells (DCs) play a key role in the antitumor immunity, as they are at the interface of innate and adaptive immunity. This important task can only be performed thanks to the broad range of mechanisms that DCs can perform to activate other immune cells. As DCs are well known for their outstanding capacity to prime and activate T cells through antigen presentation, DCs were intensively investigated during the past decades. Numerous studies have identified new DC subsets, leading to a large variety of subsets commonly separated into cDC1, cDC2, pDCs, mature DCs, Langerhans cells, monocyte-derived DCs, Axl-DCs, and several other subsets. Here, we review the specific phenotypes, functions, and localization within the tumor microenvironment (TME) of human DC subsets thanks to flow cytometry and immunofluorescence but also with the help of high-output technologies such as single-cell RNA sequencing and imaging mass cytometry (IMC).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Van Voorhis W, Hair L, Steinman R et al (1982) Human dendritic cells. Enrichment and characterization from peripheral blood. J Exp Med 155:1172–1187

    Article  PubMed  PubMed Central  Google Scholar 

  2. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511

    Article  CAS  PubMed  Google Scholar 

  3. Piqueras B, Connolly J, Freitas H et al (2006) Upon viral exposure, myeloid and plasmacytoid dendritic cells produce 3 waves of distinct chemokines to recruit immune effectors. Blood 107:2613–2618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Paul WE (2011) Bridging innate and adaptive immunity. Cell 147:1212–1215

    Article  CAS  PubMed  Google Scholar 

  5. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252

    Article  CAS  PubMed  Google Scholar 

  6. Villani A-C, Satija R, Reynolds G et al (2017) Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science 356:eaah4573

    Article  PubMed  PubMed Central  Google Scholar 

  7. Dress RJ, Dutertre C-A, Giladi A et al (2019) Plasmacytoid dendritic cells develop from Ly6D + lymphoid progenitors distinct from the myeloid lineage. Nat Immunol 20:852–864

    Article  CAS  PubMed  Google Scholar 

  8. Musumeci A, Lutz K, Winheim E et al (2019) What makes a pDC: recent advances in understanding Plasmacytoid DC development and heterogeneity. Front Immunol 10:1222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. León B, López-Bravo M, Ardavín C (2007) Monocyte-derived dendritic cells formed at the infection site control the induction of protective T helper 1 responses against Leishmania. Immunity 26:519–531

    Article  PubMed  Google Scholar 

  10. Sancho D, Joffre OP, Keller AM et al (2009) Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature 458:899–903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ahrens S, Zelenay S, Sancho D et al (2012) F-actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells. Immunity 36:635–645

    Article  CAS  PubMed  Google Scholar 

  12. Zhang J-G, Czabotar PE, Policheni AN et al (2012) The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments. Immunity 36:646–657

    Article  CAS  PubMed  Google Scholar 

  13. Théry C, Amigorena S (2001) The cell biology of antigen presentation in dendritic cells. Curr Opin Immunol 13:45–51

    Article  PubMed  Google Scholar 

  14. Schulz O, Diebold SS, Chen M et al (2005) Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature 433:887–892

    Article  CAS  PubMed  Google Scholar 

  15. Haniffa M, Shin A, Bigley V et al (2012) Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells. Immunity 37:60–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hubert M, Gobbini E, Couillault C et al (2020) IFN-III is selectively produced by cDC1 and predicts good clinical outcome in breast cancer. Sci Immunol 5:eaav3942

    Article  CAS  PubMed  Google Scholar 

  17. Böttcher JP, Bonavita E, Chakravarty P et al (2018) NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell 172:1022–1037.e14

    Article  PubMed  PubMed Central  Google Scholar 

  18. Galibert L, Diemer GS, Liu Z et al (2005) Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-I-restricted T-cell-associated molecule * ♦. J Biol Chem 280:21955–21964

    Article  CAS  PubMed  Google Scholar 

  19. Arase N, Takeuchi A, Unno M et al (2005) Heterotypic interaction of CRTAM with Necl2 induces cell adhesion on activated NK cells and CD8+ T cells. Int Immunol 17:1227–1237

    Article  CAS  PubMed  Google Scholar 

  20. Boles KS, Barchet W, Diacovo T et al (2005) The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell responses through the cell-surface receptor CRTAM. Blood 106:779–786

    Article  CAS  PubMed  Google Scholar 

  21. Zhang L, Li Z, Skrzypczynska KM et al (2020) Single-cell analyses inform mechanisms of myeloid-targeted therapies in colon cancer. Cell 181:442–459.e29

    Article  CAS  PubMed  Google Scholar 

  22. Jongbloed SL, Kassianos AJ, McDonald KJ 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 207:1247–1260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Poulin LF, Salio M, Griessinger E et al (2010) Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells. J Exp Med 207:1261–1271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Miller JC, Brown BD, Shay T et al (2012) Deciphering the transcriptional network of the dendritic cell lineage. Nat Immunol 13:888–899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Guermonprez P, Valladeau J, Zitvogel L et al (2002) Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol 20:621–667

    Article  CAS  PubMed  Google Scholar 

  26. Hémont C, Neel A, Heslan M et al (2013) Human blood mDC subsets exhibit distinct TLR repertoire and responsiveness. J Leukoc Biol 93:599–609

    Article  PubMed  Google Scholar 

  27. Collin M, Bigley V (2018) Human dendritic cell subsets: an update. Immunology 154:3–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. ** J-O, Zhang W, Du J et al (2014) BDCA1-positive dendritic cells (DCs) represent a unique human myeloid DC subset that induces innate and adaptive immune responses to Staphylococcus aureus infection. Infect Immun 82:4466–4476

    Article  PubMed  PubMed Central  Google Scholar 

  29. Nizzoli G, Krietsch J, Weick A et al (2013) Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses. Blood 122:932–942

    Article  CAS  PubMed  Google Scholar 

  30. Sittig SP, Bakdash G, Weiden J, et al (2016) A comparative study of the T Cell stimulatory and polarizing capacity of human primary blood dendritic cell subsets. Mediators Inflamm 2016:3605643

    Google Scholar 

  31. Blasio SD, Wortel IMN, van Bladel DAG et al (2016) Human CD1c+ DCs are critical cellular mediators of immune responses induced by immunogenic cell death. OncoImmunology 5:e1192739

    Article  PubMed  PubMed Central  Google Scholar 

  32. 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 210:1035–1047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cohn L, Chatterjee B, Esselborn F et al (2013) Antigen delivery to early endosomes eliminates the superiority of human blood BDCA3+ dendritic cells at cross presentation. J Exp Med 210:1049–1063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Alcántara-Hernández M, Leylek R, Wagar LE et al (2017) High-dimensional phenotypic map** of human dendritic cells reveals interindividual variation and tissue specialization. Immunity 47:1037–1050.e6

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kim N, Kim HK, Lee K et al (2020) Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma. Nat Commun 11:1–5

    Google Scholar 

  36. Klareskog L, Tjernlund UM, Forsum U et al (1977) Epidermal Langerhans cells express Ia antigens. Nature 268:248–250

    Article  CAS  PubMed  Google Scholar 

  37. Valladeau J, Ravel O, Dezutter-Dambuyant C et al (2000) Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 12:71–81

    Article  CAS  PubMed  Google Scholar 

  38. Cella M, Jarrossay D, Facchetti F et al (1999) Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med 5:919–923

    Article  CAS  PubMed  Google Scholar 

  39. Siegal FP, Kadowaki N, Shodell M et al (1999) The nature of the principal type 1 interferon-producing cells in human blood. Science 284:1835–1837

    Article  CAS  PubMed  Google Scholar 

  40. Alculumbre SG, Saint-André V, Di Domizio J et al (2018) Diversification of human plasmacytoid predendritic cells in response to a single stimulus. Nat Immunol 19:63–75

    Article  CAS  PubMed  Google Scholar 

  41. Ladányi A, Kiss J, Somlai B et al (2007) Density of DC-LAMP+ mature dendritic cells in combination with activated T lymphocytes infiltrating primary cutaneous melanoma is a strong independent prognostic factor. Cancer Immunol Immunother 56:1459–1469

    Article  PubMed  Google Scholar 

  42. León B, López-Bravo M, Ardavín C (2005) Monocyte-derived dendritic cells. Semin Immunol 17:313–318

    Article  PubMed  Google Scholar 

  43. Bakdash G, Buschow SI, Gorris MAJ et al (2016) Expansion of a BDCA1+CD14+ myeloid cell population in melanoma patients may attenuate the efficacy of dendritic cell vaccines. Cancer Res 76:4332–4346

    Article  CAS  PubMed  Google Scholar 

  44. See P, Dutertre C-A, Chen J et al (2017) Map** the human DC lineage through the integration of high-dimensional techniques. Science 356:eaag3009

    Article  PubMed  PubMed Central  Google Scholar 

  45. Gerhard GM, Bill R, Messemaker M et al (2021) Tumor-infiltrating dendritic cell states are conserved across solid human cancers. J Exp Med 218:e20200264

    Article  CAS  PubMed  Google Scholar 

  46. Broz ML, Binnewies M, Boldajipour B et al (2014) Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell 26:638–652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Salmon H, Idoyaga J, Rahman A 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 44:924–938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hildner K, Edelson BT, Purtha WE et al (2008) Batf3 deficiency reveals a critical role for CD8α+ dendritic cells in cytotoxic T cell immunity. Science 322:1097–1100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Poulin LF, Reyal Y, Uronen-Hansson H et al (2012) DNGR-1 is a specific and universal marker of mouse and human Batf3-dependent dendritic cells in lymphoid and nonlymphoid tissues. Blood 119:6052–6062

    Article  CAS  PubMed  Google Scholar 

  50. Hammerich L, Marron TU, Upadhyay R et al (2019) Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination. Nat Med 25:814–824

    Article  CAS  PubMed  Google Scholar 

  51. Maier B, Leader AM, Chen ST et al (2020) A conserved dendritic-cell regulatory program limits antitumour immunity. Nature 580:257–262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Sánchez-Paulete AR, Teijeira A, Cueto FJ et al (2017) Antigen cross-presentation and T-cell cross-priming in cancer immunology and immunotherapy. Ann Oncol 28:xii44–xii55

    Article  PubMed  Google Scholar 

  53. Wculek SK, Cueto FJ, Mujal AM et al (2020) Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol 20:7–24

    Article  CAS  PubMed  Google Scholar 

  54. Barry KC, Hsu J, Broz ML et al (2018) A natural killer–dendritic cell axis defines checkpoint therapy–responsive tumor microenvironments. Nat Med 24:1178–1191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Dikshit A, Anderson CM, Zhang B et al (2020) Conventional type 1 dendritic cells and natural killer cells demonstrate strong correlation to cytotoxic T lymphocyte infiltration in cervical cancer tumors. J Immunol 204:243.11

    Article  Google Scholar 

  56. Peterson EE, Barry KC (2020) The natural killer-dendritic cell immune axis in anti-cancer immunity and immunotherapy. Front Immunol 11:621254

    Article  CAS  PubMed  Google Scholar 

  57. Bödder J, Zahan T, van Slooten R et al (2021) Harnessing the cDC1-NK cross-talk in the tumor microenvironment to battle cancer. Front Immunol 11:631713

    Article  PubMed  PubMed Central  Google Scholar 

  58. Deauvieau F, Ollion V, Doffin A-C et al (2015) Human natural killer cells promote cross-presentation of tumor cell-derived antigens by dendritic cells: NK Cells Promote Cross-Presentation of Antigens. Int J Cancer 136:1085–1094

    Article  CAS  PubMed  Google Scholar 

  59. Lauterbach H, Bathke B, Gilles S et al (2010) Mouse CD8α+ DCs and human BDCA3+ DCs are major producers of IFN-λ in response to poly IC. J Exp Med 207:2703–2717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Yoshio S, Kanto T, Kuroda S et al (2013) Human blood dendritic cell antigen 3 (BDCA3)+ dendritic cells are a potent producer of interferon-λ in response to hepatitis C virus. Hepatology 57:1705–1715

    Article  CAS  PubMed  Google Scholar 

  61. Balan S, Ollion V, Colletti N 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 193:1622–1635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Binnewies M, Mujal AM, Pollack JL et al (2019) Unleashing type-2 dendritic cells to drive protective antitumor CD4+ T cell immunity. Cell 177:556–571.e16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Santegoets SJ, Duurland CL, Jordanova EJ et al (2020) CD163+ cytokine-producing cDC2 stimulate intratumoral type 1 T cell responses in HPV16-induced oropharyngeal cancer. J Immunother Cancer 8:e001053

    Article  PubMed  PubMed Central  Google Scholar 

  64. Michea P, Noël F, Zakine E et al (2018) Adjustment of dendritic cells to the breast-cancer microenvironment is subset specific. Nat Immunol 19:885–897

    Article  CAS  PubMed  Google Scholar 

  65. Dunn GP, Bruce AT, Sheehan KCF et al (2005) A critical function for type I interferons in cancer immunoediting. Nat Immunol 6:722–729

    Article  CAS  PubMed  Google Scholar 

  66. Katlinski KV, Gui J, Katlinskaya YV et al (2017) Inactivation of interferon receptor promotes the establishment of immune privileged tumor microenvironment. Cancer Cell 31:194–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Castiello L, Sestili P, Schiavoni G et al (2018) Disruption of IFN-I signaling promotes HER2/Neu tumor progression and breast cancer stem cells. Cancer Immunol Res 6:658–670

    Article  CAS  PubMed  Google Scholar 

  68. Gresser I, Belardelli F (2002) Endogenous type I interferons as a defense against tumors. Cytokine Growth Factor Rev 13:111–118

    Article  CAS  PubMed  Google Scholar 

  69. Zitvogel L, Galluzzi L, Kepp O et al (2015) Type I interferons in anticancer immunity. Nat Rev Immunol 15:405–414

    Article  CAS  PubMed  Google Scholar 

  70. Asmana Ningrum R (2014) Human interferon alpha-2b: a therapeutic protein for cancer treatment. Scientifica 2014:970315

    Google Scholar 

  71. Sprooten J, Agostinis P, Garg AD (2019) Type I interferons and dendritic cells in cancer immunotherapy. Int Rev Cell Mol Biol 348:217–262

    Article  CAS  PubMed  Google Scholar 

  72. Sisirak V, Faget J, Gobert M et al (2012) Impaired IFN-α production by plasmacytoid dendritic cells favors regulatory T-cell expansion that may contribute to breast cancer progression. Cancer Res 72:5188–5197

    Article  CAS  PubMed  Google Scholar 

  73. Labidi-Galy SI, Treilleux I, Goddard-Leon S et al (2012) Plasmacytoid dendritic cells infiltrating ovarian cancer are associated with poor prognosis. OncoImmunology 1:380–382

    Article  PubMed  PubMed Central  Google Scholar 

  74. Hartmann E, Wollenberg B, Rothenfusser S et al (2003) Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. Cancer Res 63:6478–6487

    CAS  PubMed  Google Scholar 

  75. Terra M, Oberkampf M, Fayolle C et al (2018) Tumor-derived TGFβ alters the ability of plasmacytoid dendritic cells to respond to innate immune signaling. Cancer Res 78:3014–3026

    Article  CAS  PubMed  Google Scholar 

  76. Perrot I, Blanchard D, Freymond N et al (2007) Dendritic cells infiltrating human non-small cell lung cancer are blocked at immature stage. J Immunol 178:2763–2769

    Article  CAS  PubMed  Google Scholar 

  77. Dey M, Chang AL, Miska J et al (2015) Dendritic cell–based vaccines that utilize myeloid rather than plasmacytoid cells offer a superior survival advantage in malignant glioma. J Immunol 195:367–376

    Article  CAS  PubMed  Google Scholar 

  78. Faget J, Bendriss-Vermare N, Gobert M et al (2012) ICOS-ligand expression on plasmacytoid dendritic cells supports breast cancer progression by promoting the accumulation of immunosuppressive CD4+ T cells. Cancer Res 72:6130–6141

    Article  CAS  PubMed  Google Scholar 

  79. Conrad C, Gregorio J, Wang Y-H et al (2012) Plasmacytoid dendritic cells promote immunosuppression in ovarian cancer via ICOS costimulation of Foxp3(+) T-regulatory cells. Cancer Res 72:5240–5249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Huang X-M, Liu X-S, Lin X-K et al (2014) Role of plasmacytoid dendritic cells and inducible costimulator-positive regulatory T cells in the immunosuppression microenvironment of gastric cancer. Cancer Sci 105:150–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Pedroza-Gonzalez A, Zhou G, Vargas-Mendez E et al (2015) Tumor-infiltrating plasmacytoid dendritic cells promote immunosuppression by Tr1 cells in human liver tumors. Onco Targets Ther 4:e1008355

    Google Scholar 

  82. Treilleux I, Blay J-Y, Bendriss-Vermare N et al (2004) Dendritic cell infiltration and prognosis of early stage breast cancer. Clin Cancer Res 10:7466–7474

    Article  CAS  PubMed  Google Scholar 

  83. Gousias K, von Ruecker A, Voulgari P et al (2013) Phenotypical analysis, relation to malignancy and prognostic relevance of ICOS+T regulatory and dendritic cells in patients with gliomas. J Neuroimmunol 264:84–90

    Article  CAS  PubMed  Google Scholar 

  84. Aspord C, Leccia M-T, Charles J et al (2013) Plasmacytoid dendritic cells support melanoma progression by promoting Th2 and regulatory immunity through OX40L and ICOSL. Cancer Immunol Res 1:402–415

    Article  CAS  PubMed  Google Scholar 

  85. Di Domizio J, Blum A, Gallagher-Gambarelli M et al (2009) TLR7 stimulation in human plasmacytoid dendritic cells leads to the induction of early IFN-inducible genes in the absence of type I IFN. Blood 114:1794–1802

    Article  PubMed  Google Scholar 

  86. Movassagh M, Spatz A, Davoust J et al (2004) Selective accumulation of mature DC-Lamp + dendritic cells in tumor sites is associated with efficient T-cell-mediated antitumor response and control of metastatic dissemination in melanoma. Cancer Res 64:2192–2198

    Article  CAS  PubMed  Google Scholar 

  87. Dieu-Nosjean M-C, Antoine M, Danel C et al (2008) Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol 26:4410–4417

    Article  CAS  PubMed  Google Scholar 

  88. Sautès-Fridman C, Cherfils-Vicini J, Damotte D et al (2011) Tumor microenvironment is multifaceted. Cancer Metastasis Rev 30:13–25

    Article  PubMed  Google Scholar 

  89. Dieu-Nosjean M-C, Giraldo NA, Kaplon H et al (2016) Tertiary lymphoid structures, drivers of the anti-tumor responses in human cancers. Immunol Rev 271:260–275

    Article  CAS  PubMed  Google Scholar 

  90. Sautès-Fridman C, Lawand M, Giraldo NA et al (2016) Tertiary lymphoid structures in cancers: prognostic value, regulation, and manipulation for therapeutic intervention. Front Immunol 7:407

    Article  PubMed  PubMed Central  Google Scholar 

  91. Truxova I, Kasikova L, Hensler M et al (2018) Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients. J Immunother Cancer 6:139

    Article  PubMed  PubMed Central  Google Scholar 

  92. Zilionis R, Engblom C, Pfirschke C et al (2019) Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species. Immunity 50:1317–1334.e10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Qian J, Olbrecht S, Boeckx B et al (2020) A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling. Cell Res 30:745–762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Qian B-Z, Li J, Zhang H et al (2011) CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475:222–225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Shand FHW, Ueha S, Otsuji M et al (2014) Tracking of intertissue migration reveals the origins of tumor-infiltrating monocytes. Proc Natl Acad Sci U S A 111:7771–7776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Sánchez-Paulete AR, Cueto FJ, Martínez-López M et al (2016) Cancer immunotherapy with immunomodulatory anti-CD137 and anti–PD-1 monoclonal antibodies requires BATF3-dependent dendritic cells. Cancer Discov 6:71–79

    Article  PubMed  Google Scholar 

  97. Segura E, Touzot M, Bohineust A et al (2013) Human inflammatory dendritic cells induce Th17 cell differentiation. Immunity 38:336–348

    Article  CAS  PubMed  Google Scholar 

  98. Bourdely P, Anselmi G, Vaivode K et al (2020) Transcriptional and functional analysis of CD1c+ human dendritic cells identifies a CD163+ subset priming CD8+CD103+ T cells. Immunity 53:335–352.e8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Shevchuk Z, Filip A, Shevchuk V et al (2014) Number of Langerhans cells is decreased in premalignant keratosis and skin cancers. Exp Oncol 36:34–37

    CAS  PubMed  Google Scholar 

  100. Tsuge T, Yamakawa M, Tsukamoto M (2000) Infiltrating dendritic/Langerhans cells in primary breast cancer. Breast Cancer Res Treat 59:141–152

    Article  CAS  PubMed  Google Scholar 

  101. Bigotti G, Coli A, Castagnola D (1991) Distribution of langerhans cells and HLA class II molecules in prostatic carcinomas of different histopathological grade. Prostate 19:73–87

    Article  CAS  PubMed  Google Scholar 

  102. Tsujitani S, Furukawa T, Tamada R et al (1987) Langerhans cells and prognosis in patients with gastric carcinoma. Cancer 59:501–505

    Article  CAS  PubMed  Google Scholar 

  103. Manickam A, Sivanandham M, Tourkova IL (2007) Immunological role of dendritic cells in cervical cancer. Adv Exp Med Biol 601:155–162

    Article  PubMed  Google Scholar 

  104. Kindt N, Descamps G, Seminerio I et al (2016) Langerhans cell number is a strong and independent prognostic factor for head and neck squamous cell carcinomas. Oral Oncol 62:1–10

    Article  PubMed  Google Scholar 

  105. Rajesh A, Hibma M (2020) Novel concepts: Langerhans cells in the tumour microenvironment. In: Birbrair A (ed) Tumor microenvironment. Springer International Publishing, Cham, pp 147–158

    Chapter  Google Scholar 

  106. Peña-Cruz V, McDonough SM, Diaz-Griffero F et al (2010) PD-1 on immature and PD-1 ligands on migratory human Langerhans cells regulate antigen-presenting cell activity. J Invest Dermatol 130:2222–2230

    Article  PubMed  PubMed Central  Google Scholar 

  107. Nakano T, Oka K, Takahashi T et al (1992) Roles of Langerhans’ cells and T-lymphocytes infiltrating cancer tissues in patients treated by radiation therapy for cervical cancer. Cancer 70:2839–2844

    Article  CAS  PubMed  Google Scholar 

  108. Hillenbrand EE, Neville AM, Coventry BJ (1999) Immunohistochemical localization of CD1a-positive putative dendritic cells in human breast tumours. Br J Cancer 79:940–944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Iwamoto M, Shinohara H, Miyamoto A et al (2003) Prognostic value of tumor-infiltrating dendritic cells expressing CD83 in human breast carcinomas. Int J Cancer 104:92–97

    Article  CAS  PubMed  Google Scholar 

  110. Coventry BJ, Morton J (2003) CD1a-positive infiltrating-dendritic cell density and 5-year survival from human breast cancer. Br J Cancer 89:533–538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Tabarkiewicz J, Rybojad P, Jablonka A et al (2008) CD1c+ and CD303+ dendritic cells in peripheral blood, lymph nodes and tumor tissue of patients with non-small cell lung cancer. Oncol Rep 19:237–243

    PubMed  Google Scholar 

  112. Sandel MH, Dadabayev AR, Menon AG et al (2005) Prognostic value of tumor-infiltrating dendritic cells in colorectal cancer: role of maturation status and intratumoral localization. Clin Cancer Res 11:2576–2582

    Article  CAS  PubMed  Google Scholar 

  113. Goldman SA, Baker E, Weyant RJ et al (1998) Peritumoral CD1a-positive dendritic cells are associated with improved survival in patients with tongue carcinoma. Arch Otolaryngol Head Neck Surg 124:641–646

    Article  CAS  PubMed  Google Scholar 

  114. Schwaab T, Schned AR, Heaney JA et al (1999) In vivo description of dendritic cells in human renal cell carcinoma. J Urol 162:567–573

    Article  CAS  PubMed  Google Scholar 

  115. Martinet L, Filleron T, Le Guellec S et al (2013) High endothelial venule blood vessels for tumor-infiltrating lymphocytes are associated with lymphotoxin β-producing dendritic cells in human breast cancer. J Immunol Baltim MD 1950 191:2001–2008

    CAS  Google Scholar 

  116. Ishigami S, Natsugoe S, Hokita S et al (2000) Intranodal antitumor immunocyte infiltration in node-negative gastric cancers. Clin Cancer Res 6:2611–2617

    CAS  PubMed  Google Scholar 

  117. Labidi-Galy SI, Sisirak V, Meeus P et al (2011) Quantitative and functional alterations of plasmacytoid dendritic cells contribute to immune tolerance in ovarian cancer. Cancer Res 71:5423–5434

    Article  CAS  PubMed  Google Scholar 

  118. Oshi M, Newman S, Tokumaru Y et al (2020) Plasmacytoid dendritic cell (pDC) infiltration correlate with tumor infiltrating lymphocytes, cancer immunity, and better survival in triple negative breast cancer (TNBC) more strongly than conventional dendritic cell (cDC). Cancers 12:E3342

    Article  Google Scholar 

  119. Kießler M, Plesca I, Sommer U et al (2021) Tumor-infiltrating plasmacytoid dendritic cells are associated with survival in human colon cancer. J Immunother Cancer 9:e001813

    Article  PubMed  PubMed Central  Google Scholar 

  120. Elaldi R, Hemon P, Petti L et al (2021) High dimensional imaging mass cytometry panel to visualize the tumor immune microenvironment contexture. Front Immunol 12:666233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Ijsselsteijn ME, van der Breggen R, Farina Sarasqueta A et al (2019) A 40-marker panel for high dimensional characterization of cancer immune microenvironments by imaging mass cytometry. Front Immunol 10:2534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Halliday GM, Patel A, Hunt MJ et al (1995) Spontaneous regression of human melanoma/nonmelanoma skin cancer: association with infiltrating CD4+ T cells. World J Surg 19:352–358

    Article  CAS  PubMed  Google Scholar 

  123. Krummel MF, Allison JP (1995) CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 182:459–465

    Article  CAS  PubMed  Google Scholar 

  124. Krummel MF, Allison JP (1996) CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J Exp Med 183:2533–2540

    Article  CAS  PubMed  Google Scholar 

  125. Leach DR, Krummel MF, Allison JP (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science 271:1734–1736

    Article  CAS  PubMed  Google Scholar 

  126. Hurwitz AA, Yu TF, Leach DR et al (1998) CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc Natl Acad Sci U S A 95:10067–10071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. van Elsas A, Hurwitz AA, Allison JP (1999) Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med 190:355–366

    Article  PubMed  PubMed Central  Google Scholar 

  128. Pentcheva-Hoang T, Egen JG, Wojnoonski K et al (2004) B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse. Immunity 21:401–413

    Article  CAS  PubMed  Google Scholar 

  129. Peggs KS, Quezada SA, Chambers CA et al (2009) Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med 206:1717–1725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Yost KE, Satpathy AT, Wells DK et al (2019) Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat Med 25:1251–1259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Azizi E, Carr AJ, Plitas G et al (2018) Single-cell map of diverse immune phenotypes in the breast tumor microenvironment. Cell 174:1293–1308.e36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Cillo AR, Kürten CHL, Tabib T et al (2020) Immune landscape of viral- and carcinogen-driven head and neck cancer. Immunity 52:183–199.e9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Neal JT, Li X, Zhu J et al (2018) Organoid modeling of the tumor immune microenvironment. Cell 175:1972–1988.e16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Yuen KC, Liu L-F, Gupta V et al (2020) High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade. Nat Med 26:693–698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Zhang Q, He Y, Luo N et al (2019) Landscape and dynamics of single immune cells in hepatocellular carcinoma. Cell 179:829–845.e20

    Article  CAS  PubMed  Google Scholar 

  136. Paulson KG, Voillet V, McAfee MS et al (2018) Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA. Nat Commun 9:3868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Song Q, Hawkins GA, Wudel L et al (2019) Dissecting intratumoral myeloid cell plasticity by single cell RNA-seq. Cancer Med 8:3072–3085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Li H, van der Leun AM, Yofe I et al (2019) Dysfunctional CD8 T cells form a proliferative, dynamically regulated compartment within human melanoma. Cell 176:775–789.e18

    Article  CAS  PubMed  Google Scholar 

  139. Sade-Feldman M, Yizhak K, Bjorgaard SL et al (2018) Defining T cell states associated with response to checkpoint immunotherapy in melanoma. Cell 175:998–1013.e20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Nirschl CJ, Suárez-Fariñas M, Izar B et al (2017) IFNγ-dependent tissue-immune homeostasis is co-opted in the tumor microenvironment. Cell 170:127–141.e15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Ji AL, Rubin AJ, Thrane K et al (2020) Multimodal analysis of composition and spatial architecture in human squamous cell carcinoma. Cell 182:497–514.e22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Brown CC, Gudjonson H, Pritykin Y et al (2019) Transcriptional basis of mouse and human dendritic cell heterogeneity. Cell 179:846–863.e24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Univ Lyon, Université Claude Bernard Lyon 1, INSERM U1052, CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France

    Candice Sakref, Nathalie Bendriss-Vermare & Jenny Valladeau-Guilemond

  2. LabEx DEVweCAN, Lyon, France

    Candice Sakref, Nathalie Bendriss-Vermare & Jenny Valladeau-Guilemond

  3. Laboratoire d’Immunothérapie des Cancers de Lyon (LICL), Lyon, France

    Nathalie Bendriss-Vermare

Authors
  1. Candice Sakref
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nathalie Bendriss-Vermare
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jenny Valladeau-Guilemond
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jenny Valladeau-Guilemond .

Editor information

Editors and Affiliations

  1. UMR CNRS 5164 – Immunoconcept, Université de Bordeaux, Bordeaux, France

    Vanja Sisirak

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Sakref, C., Bendriss-Vermare, N., Valladeau-Guilemond, J. (2023). Phenotypes and Functions of Human Dendritic Cell Subsets in the Tumor Microenvironment. In: Sisirak, V. (eds) Dendritic Cells. Methods in Molecular Biology, vol 2618. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2938-3_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-2938-3_2

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2937-6

  • Online ISBN: 978-1-0716-2938-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation