Skip to main content

Advertisement

SpringerLink
Log in

Maturation of circulating dendritic cells and imbalance of T-cell subsets in patients with squamous cell carcinoma of the head and neck

  • Original Article
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Interactions between dendritic cells (DCs) and T cells play a pivotal role in the regulation and maintenance of immune responses. In cancer patients, various immunological abnormalities have been observed in these immune cells. Here, we investigated proportions and the phenotype of DCs and the cytokine profile of T-cell subsets in the peripheral blood of patients with squamous cell carcinoma of the head and neck (SCCHN), using multicolor flow cytometry. The percentage of myeloid (CD11c+), but not plasmacytoid (CD123+) DCs, was significantly lower (P<0.05) and expression of HLA-DR was significantly decreased in total and myeloid DCs of cancer patients compared to healthy donors. Simultaneous analyses of T-cell subsets in the patients’ circulation showed significantly increased proportions of CD4+ T cells expressing Th1 and Th2 cytokines after ex vivo stimulation without any skewing in the Th1/Th2 ratio. The relative level of HLA-DR expression on myeloid or total DCs positively correlated with the Th1/Th2 ratio (P<0.01), and the proportion of total circulating DCs was inversely correlated with that of regulatory CD4+CD25+ T cells (P<0.01). These results suggest that the decreased proportion of circulating DCs and decreased HLA-DR expression in DCs may have a major impact on systemic immune responses in patients with SCCHN.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Hadden JW (1997) The immunopharmacology of head and neck cancer: an update. Int J Immunopharmacol 11/12:629–644

    Google Scholar 

  2. Richtsmeier WJ (1997) Immunology of head and neck cancer. Bull Am Coll Surg 82:32–53

    Google Scholar 

  3. Almand B, Resser JR, Lindman B, Nadaf S, Clark JI, Kwon ED, Carbone DP, Gabrilovich DI (2000) Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res 6:1755–1766

    PubMed  CAS  Google Scholar 

  4. Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI (2001) Increased production of immature myeloid cells in cancer patients: A mechanism of immunosuppression in cancer. J Immunol 166:678–689

    PubMed  CAS  Google Scholar 

  5. Ratta M, Fagnoni F, Curti A, Vescovini R, Sansoni P, Oliviero B, Fogli M, Ferri E, Della Cuna GR, Tura S, Baccarani M, Lemoli RM (2002) Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood 100:230–237

    Article  PubMed  CAS  Google Scholar 

  6. Reichert TE, Strauss L, Wagner EM, Gooding W, Whiteside TL (2002) Signaling abnormalities, apoptosis, and reduced proliferation of circulating and tumor-infiltrating lymphocytes in patients with oral carcinoma. Clin Cancer Res 8:3137–3145

    PubMed  Google Scholar 

  7. Kuss I, Saito T, Johnson JT (1999) Clinical significance of decreased ζ chain expression in peripheral blood lymphocytes of patients with head and neck cancer. Clin Cancer Res 5:329–334

    PubMed  CAS  Google Scholar 

  8. Saito T, Kuss I, Dworacki G, Gooding W, Johnson JT, Whiteside TL (1999) Spontaneous ex vivo apoptosis of peripheral blood mononuclear cells in patients with head and neck cancer. Clin Cancer Res 5:1263–1273

    PubMed  CAS  Google Scholar 

  9. Shibuya TY, Nugyen N, McLaren CE, Li KT, Wei WZ, Kim S, Yoo GH, Rogowski A, Ensley J, Sakr W (2002) Clinical significance of poor CD3 response in head and neck cancer. Clin Cancer Res 8:745–751

    PubMed  CAS  Google Scholar 

  10. Lathers DMR, Achille NJ, Young MRI (2003) Incomplete Th2 skewing of cytokines in plasma of patients with squamous cell carcinoma of the head and neck. Hum Immunol 64:1160–1166

    Article  PubMed  CAS  Google Scholar 

  11. Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, Rubin SC, Kaiser LR, June CH (2001) Regulatory CD4+CD25+ T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 61:4766–4772

    PubMed  CAS  Google Scholar 

  12. Sasada T, Kimura M, Yoshida Y, Kanai M, Takabayashi A (2003) CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies. Cancer 98:1089–1099

    Article  PubMed  Google Scholar 

  13. Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E (2003) Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 9:606–612

    PubMed  Google Scholar 

  14. Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 193:233–238

    Article  PubMed  CAS  Google Scholar 

  15. Hoffmann TK, Muller-Berghaus J, Ferris RL, Johnson JT (2002) Storkus W.J., Whiteside T.L. Alterations in the frequency of dendritic cell subsets in the peripheral circulation of patients with squamous cell carcinomas of the head and neck. Clin Cancer Res 8:1787–1793

    PubMed  Google Scholar 

  16. Gabrilovich D (2004) Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol 4:941–952

    Article  PubMed  CAS  Google Scholar 

  17. Schaefer C, Kim GG, Albers A, Hoermann K, Myers EN, Whiteside TL (2005) Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer. Br J Cancer (in press)

  18. Goldman SA, Baker E, Weyant RJ, Clarke MR, Myers JN, Lotze MT (1998) Peritumoral CD1a-positive dendritic cells are associated with improved survival in patients with tongue carcinoma. Arch Otolaryngol Head Neck Surg 124:641–646

    PubMed  CAS  Google Scholar 

  19. Reichert TE, Scheuer C, Day R, Wagner W, Whiteside TL (2001) The number of intratumoral dendritic cells and ζ-chain expression in T cells as prognostic and survival biomarkers in patients with oral carcinoma. Cancer 91:2136–2147

    Article  PubMed  CAS  Google Scholar 

  20. Sakakura K, Chikamatsu K, Sakurai T, Takahashi K, Murata T, Oriuchi N, Furuya N (2005) Infiltration of dendritic cells and NK cells into the sentinel lymph node in oral cavity cancer. Oral Oncol 41:89–96

    Article  PubMed  CAS  Google Scholar 

  21. Melichar B, Savary C, Kudelka AP, Verschraegen C, Kavanagh JJ, Edwards CL, Platsoucas CD, Freedman RS (1998) Lineage-negative human leukocyte antigen-DR+ cells with the phenotype of undifferentiated dendritic cells in patients with carcinoma of the abdomen and pelvis. Clin Cancer Res 4:799–809

    PubMed  CAS  Google Scholar 

  22. Lissoni P, Vigore L, Ferranti R, Bukovec R, Meregalli S, Mandala M, Barni S, Tancini G, Fumagalli L, Giani L (1999) Circulating dendritic cells in early and advanced cancer patients: diminished percent in the metastatic disease. J Biol Regul Homeost Agents 13:216–219

    PubMed  CAS  Google Scholar 

  23. Ito N, Nakamura H, Tanaka Y, Ohgi S (1999) Lung carcinoma: analysis of T helper type 1 and 2 cells and T cytotoxic type 1 and 2 cells by intracellular cytokine detection with flow cytometry. Cancer 85:2359–2367

    Article  PubMed  CAS  Google Scholar 

  24. Aoki Y, Tsuneki I, Sasaki M, Watanabe M, Sato T, Aida H, Tanaka K (2000) Analysis of Th1 and Th2 cells by intracellular cytokine detectionwith flow cytometry in patients with ovarian cancer. Gynecol Obstet Invest 50:207–211

    Article  PubMed  CAS  Google Scholar 

  25. Schondorf T, Engel H, Lindemann C, Kolhagen H, von Rucker AA, Mallmann P (1997) Cellular characteristics of peripheral blood lymphocytes and tumour-infiltrating lymphocytes in patients with gynaecological tumours. Cancer Immunol Immunother 44:88–96

    Article  PubMed  CAS  Google Scholar 

  26. Podhorecka M, Dmoszynska A, Rolinski J, Wasik E (2002) T type 1/type 2 subsets balance in B-cell chronic lymphocytic leukemia the three-color flow cytometry analysis. Leuk Res 26:657–660

    Article  PubMed  CAS  Google Scholar 

  27. Gergely L, Aleksza M, Varoczy L, Ponyi A, Sipka S, Illes A, Szegedi G (2004) Intracellular IL-4/IFN-gamma producing peripheral T lymphocyte subsets in B cell non-Hodgkin’s lymphoma patients. Eur J Haematol 72:336–341

    Article  PubMed  CAS  Google Scholar 

  28. Sato M, Goto S, Kaneko R, Ito M, Sato S, Takeuchi S (1998) Impaired production of Th1 cytokines and increased frequency of Th2 subsets in PBMC from advanced cancer patients. Anticancer Res 18:3951–3955

    PubMed  CAS  Google Scholar 

  29. Tabata T, Hazama S, Yoshino S, Oka M (1999) Th2 subset dominance among peripheral blood T lymphocytes in patients with digestive cancers. Am J Surg 177:203–208

    Article  PubMed  CAS  Google Scholar 

  30. Mori T, Takada R, Watanabe R, Okamoto S, Ikeda Y (2001) T-helper (Th)1/Th2 imbalance in patients with previously untreated B-cell diffuse large cell lymphoma. Cancer Immunol Immunother 50:566–568

    Article  PubMed  CAS  Google Scholar 

  31. Kim J-W, Tsukishiro T, Johnson JT, Whiteside TL (2004) Expression of pro- and anti-apoptotic proteins in circulating CD8+ T cells of patients with squamous cell carcinoma of the head and neck (SCCHN). Clin Cancer Res 10:5101–5110

    Article  PubMed  CAS  Google Scholar 

  32. Albers A, Kim GG, Ferris RL, DeLeo AB, Whiteside TL (2005) Immune responses to p53 in patients with cancer enrichment I tetramer+ p53 peptide-specific T cells and regulatory CD4+CD25+ cells at tumor sites. Cancer Immunol Immunother (in press)

  33. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949

    Article  PubMed  CAS  Google Scholar 

  34. Shevach EM (2001) Certified professionals: CD4+CD25+ suppressor T cells. J Exp Med 193:F41–F45

    Article  PubMed  CAS  Google Scholar 

  35. Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH (2000) Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 192:1213–1222

    Article  PubMed  CAS  Google Scholar 

  36. Roncarolo MG, Levings MK (2001) Traversari C. Differentiation of T regulatory cells by immature dendritic cells. J Exp Med 193:F5-F9

    Article  PubMed  CAS  Google Scholar 

  37. Fonteneau JF, Gilliet M, Larsson M, Dasilva I, Munz C, Liu Y-J, Bhardwaj N (2003) Activation of influenza virus-specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity. Blood 101:3520–3526

    Article  PubMed  CAS  Google Scholar 

  38. Mohty M, Olive D, Gaugler B (2004) Plasmacytoid DCs and cancer: a new role for an enigmatic cell. Trends Immunol 25:397–398

    Article  PubMed  CAS  Google Scholar 

  39. Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H, Lanzavecchia A, Colonna M (1999) Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med 5:919–923

    Article  PubMed  CAS  Google Scholar 

  40. Hartmann E, Wollenberg B, Rothenfusser S, Wagner M, Wellisch D, Mack B, Giese T, Gires O, Endres S, Hartmann g (2003) Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. Cancer Res 63:6478–6487

    PubMed  CAS  Google Scholar 

  41. Gabrilovich D, Ishida T, Oyama T, Ran S, Kravtsov V, Nadaf S, Carbone DP (1998) Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92:4150–4166

    PubMed  CAS  Google Scholar 

  42. Shurin GV, Shurin MR, Bykovskaia S, Shogan J, Lotze MT, Barksdale EM Jr (2001) Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function. Cancer Res 61:363–369

    PubMed  CAS  Google Scholar 

  43. Young MRI, Wright MA, Lozano Y, Matthew JP, Benefield J, Prechel MM (1996) Mechanisms of immune suppression in patients with head and neck cancer: influence on the immune infiltrate of the cancer. Int J Cancer 29:333–338

    Article  Google Scholar 

  44. Lissoni P, Brivio F, Ferrante R, Vigore L, Vaghi M, Fumagalli E, Bucovec R, Malugani F, Fumagalli L (2000) Circulating immature and mature dendritic cells in relation to lymphocyte subsets in patients with gastrointestinal tract cancer. Int J Biol Markers 15:22–25

    PubMed  CAS  Google Scholar 

  45. Mann EA, Spiro JD, Chen LL, Kreutzer DL (1992) Cytokine expression by head and neck squamous cell carcinomas. Am J Surg 164:567–573

    Article  PubMed  CAS  Google Scholar 

  46. Gastman BR, Johnson DE, Whiteside TL, Rabinowich H (2000) Tumor-induced apoptosis of T lymphocytes: elucidation of intracellular apoptotic events. Blood 95:2015–2023

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the ministry of Education, Science, Sports and Culture, Japan (Grants-in-Aid of Scientific Research and Priority Areas) and by NIH grant PO-1 DE12321 to T.L.W.

Author information

Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, 371-8511, Japan

    Koichi Sakakura, Kazuaki Chikamatsu, Katsumasa Takahashi & Nobuhiko Furuya

  2. Departments of Pathology, Immunology and Otolaryngology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Suite 1.27, 15213-1863, Pittsburgh, PA, USA

    Theresa L. Whiteside

Authors
  1. Koichi Sakakura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazuaki Chikamatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katsumasa Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Theresa L. Whiteside
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nobuhiko Furuya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kazuaki Chikamatsu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sakakura, K., Chikamatsu, K., Takahashi, K. et al. Maturation of circulating dendritic cells and imbalance of T-cell subsets in patients with squamous cell carcinoma of the head and neck. Cancer Immunol Immunother 55, 151–159 (2006). https://doi.org/10.1007/s00262-005-0697-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-005-0697-y

Keywords

Search

Navigation