Skip to main content
SpringerLink
Log in

Dendritic cell infiltration and prognosis of human hepatocellular carcinoma

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Aim: To elucidate the relationship between local immunocompetent cells and prognosis of human hepatocellular carcinoma (HCC) after resection. Methods: HE staining and immunohistochemical study were carried out on specimens from patients underwent surgical resection. Local immunocompetent cells, such as dendritic cells (DCs), memory T cells, CD3+ T lymphocytes and CD8+ T lymphocytes, were counted and their relationships with tumor-free survival rate were analyzed by grouping DCs with the T lymphocytes retrospectively. Results: The number grade of infiltrating immunocompetent cells in HCC nodules and pericancerous tissues under HE staining had no significant correlation with tumor-free survival time (P=0.054, 0.071, respectively). DCs were mainly among tumor cells, encircling tumor cells with their pseudopodia and were in contact with T lymphocytes. A certain number of DCs in HCC nodules (≥25/10HPF) statistically correlated to tumor-free survival time (P=0.005), while a certain number of DCs in pericancerous tissues (≥28/10HPF) had no correlation with tumor-free survival time (P=0.329). The number of memory T cells, CD3+ T lymphocytes and CD8+ T lymphocytes in HCC nodules strongly correlated to tumor-free survival time (P=0.003, 0.005, 0.037, respectively). The tumor-free survival rate curves revealed that the more DCs or together with memory T cells/CD3+ T lymphocytes or that the more CD8+ T lymphocytes were detected in HCC nodules, the better the prognosis would be. Conclusions: Marked infiltration of DCs in HCC nodules was closely related to the prognosis of HCC after surgical resection and can be served as a predictive index for recurrence and metastasis of HCC.

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

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

    Article  PubMed  CAS  Google Scholar 

  • Bethwaite PB, Holloway LJ, Thornton A, Delahunt B (1996) Infiltration by immunocompetent cells in early stage invasive carcinoma of the uterine cervix: a prognostic study. Pathology 28:321–327

    Article  PubMed  CAS  Google Scholar 

  • Chen S, Akbar SM, Tanimoto K, Ninomiya T, Iuchi H, Michitaka K, Horiike N, Onji M (2000) Absence of CD83-positive mature and activated dendritic cells at cancer nodules from patients with hepatocellular carcinoma: relevance to hepatocarcinogenesis. Cancer Lett 148:49–57

    Article  PubMed  CAS  Google Scholar 

  • Cho Y, Miyamoto M, Kato K, Fukunaga A, Shichinohe T, Kawarada Y, Hida Y, Oshikiri T, Kurokawa T, Suzuoki M, Nakakubo Y, Hiraoka K, Murakami S, Shinohara T, Itoh T, Okushiba S, Kondo S, Katoh H (2003) CD4+ and CD8+ T cells cooperate to improve prognosis of patients with esophageal squamous cell carcinoma. Cancer Res 63:1555–1559

    PubMed  CAS  Google Scholar 

  • Ciavarra RP, Holterman DA, Brown RR, Mangiotti P, Yousefieh N, Wright GL Jr, Schellhammer PF, Glass WF, Somers KD (2004) Prostate tumor microenvironment alters immune cells and prevents long-term survival in an orthotopic mouse model following flt3-ligand/CD40-ligand immunotherapy. J Immunother 27:13–26

    Article  PubMed  CAS  Google Scholar 

  • Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC, Fisher RI, Braziel RM, Rimsza LM, Grogan TM, Miller TP, LeBlanc M, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Smeland EB, Kvaloy S, Holte H, Delabie J, Connors JM, Lansdorp PM, Ouyang Q, Lister TA, Davies AJ, Norton AJ, Muller-Hermelink HK, Ott G, Campo E, Montserrat E, Wilson WH, Jaffe ES, Simon R, Yang L, Powell J, Zhao H, Goldschmidt N, Chiorazzi M, Staudt LM (2004) Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 351:2159–2169

    Article  PubMed  CAS  Google Scholar 

  • Doherty DG, O’Farrelly C (2000) Innate and adaptive lymphoid cells in the human liver. Immunol Rev 174:5–20

    Article  PubMed  CAS  Google Scholar 

  • Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nature Immunol 3:991–998

    Article  CAS  Google Scholar 

  • Eisenthal A, Polyvkin N, Bramante-Schreiber L, Misonznik F, Hassner A, Lifschitz-Mercer B (2001) Expression of dendritic cells in ovarian tumors correlates with clinical outcome in patients with ovarian cancer. Hum Pathol 32:803–807

    Article  PubMed  CAS  Google Scholar 

  • Feijoo E, Alfaro C, Mazzolini G, Serra P, Penuelas I, Arina A, Huarte E, Tirapu I, Palencia B, Murillo O, Ruiz J, Sangro B, Richter JA, Prieto J, Melero I (2005) Dendritic cells delivered inside human carcinomas are sequestered by interleukin-8. Int J Cancer 116:275–281

    Article  PubMed  CAS  Google Scholar 

  • Fidler IJ (2003) The pathogenesis of cancer metastases: the “Seed and soil” hypothesis revisited. Nat Rev Cancer 3:1–6

    Article  Google Scholar 

  • Howard L, Kaufman, Mary LD (2004) Immune system versus tumor: shifting the balance in favor of DCs and effective immunity. J Clin Invest 113:664–667

    Google Scholar 

  • Ishigami S, Natsugoe S, Matsumoto M, Okumura H, Sakita H, Nakashima S, Takao S, Aikou T (2003) Clinical implications of intratumoral dendritic cell infiltration in esophageal squamous cell carcinoma. Oncol Rep 10:1237–1240

    PubMed  Google Scholar 

  • Jewell AP (2005) Is the liver an important site for the development of immune tolerance to tumours? Med Hypotheses 64:751–754

    Article  PubMed  CAS  Google Scholar 

  • Kawata A, Une Y, Hosokawa M, Uchino J, Kobayashi H (1992) Tumor-infiltrating lymphocytes and prognosis of hepatocellular carcinoma. Jpn J Clin Oncol 22:256–263

    PubMed  CAS  Google Scholar 

  • Lespagnard L, Gancberg D, Rouas G, Leclercq G, de Saint-Aubain Somerhausen N, Di Leo A, Piccart M, Verhest A, Larsimont D (1999) Tumor-infiltrating dendritic cells in adenocarcinomas of the breast: a study of 143 neoplasms with a correlation to usual prognostic factors and to clinical outcome. Int J Cancer 84:309–314

    Article  PubMed  CAS  Google Scholar 

  • Liotta LA, Kohn EC (2001) The microenvironment of the tumor-host interface. Nature 411:375–379

    Article  PubMed  CAS  Google Scholar 

  • Ludewig B, Oehen S, Barchiesi F, Schwendener RA, Hengartner H, Zinkernagel RM (1999) Protective antiviral cytotoxic T cell memory is most efficiently maintained by restimulation via dendritic cells. J Immunol 163:1839–1844

    PubMed  CAS  Google Scholar 

  • Miyagawa S, Soeda J, Takagi S, Miwa S, Ichikawa E, Noike T (2004) Prognostic significance of mature dendritic cells and factors associated with their accumulation in metastatic liver tumors from colorectal cancer. Hum Pathol 35:1392–1396

    Article  PubMed  Google Scholar 

  • Nakano O, Sato M, Naito Y, Suzuki K, Orikasa S, Aizawa M, Suzuki Y, Shintaku I, Nagura H, Ohtani H (2001) Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res 61:5132–5136

    PubMed  CAS  Google Scholar 

  • Ninomiya T, Akbar SM, Masumoto T, Horiike N, Onji M (1999) Dendritic cells with immature phenotype and defective function in the peripheral blood from patients with hepatocellular carcinoma. J Hepatol 31:323–331

    Article  PubMed  CAS  Google Scholar 

  • Norris S, Collins C, Doherty DG, Smith F, McEntee G, Traynor O, Nolan N, Hegarty J, O’Farrelly C (1998) Resident human hepatic lymphocytes are phenotypically different from circulating lymphocytes. J Hepatol 28:84–90

    Article  PubMed  CAS  Google Scholar 

  • O’Beirne JP, Harrison PM (2004) The role of the immune system in the control of hepatocellular carcinoma. Eur J Gastroenterol Hepatol 16:1257–1260

    Article  PubMed  Google Scholar 

  • Qin J, Han B, Pang J (1997) The relationship between TIL from human primary hepatic carcinoma and prognosis (Chin). Zhonghua Yi Xue Za Zhi 77(3):167–70

    PubMed  CAS  Google Scholar 

  • Rosenberg SA (2001) Progress in human tumour immunology and immunotherapy. Nature 411:380–384

    Article  PubMed  CAS  Google Scholar 

  • Srivastava PK (2000) Immunotherapy of human cancer: lessons from mice. Nat Immunol 1:363–366

    Article  PubMed  CAS  Google Scholar 

  • Starzl TE (2001) The “privileged” liver and hepatic tolerogenicity. Liver Transpl 7:918–920

    Article  PubMed  CAS  Google Scholar 

  • Steinman RM (1999) Dendritic cells In: Paul WE (ed) Fundamental immunology, 4th ed. Lippincott-Raven Publishers, Philadelphia, pp 547–573

    Google Scholar 

  • Steinman RM (2000) DC-SIGN: a guide to some mysteries of dendritic cells. Cell 100:491–494

    Article  PubMed  CAS  Google Scholar 

  • Steinman RM, Nussenzweig MC (2002) Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci USA 99:351–358

    Article  PubMed  CAS  Google Scholar 

  • Unitt E, Rushbrook SM, Marshall A, Davies S, Gibbs P, Morris LS, Coleman N, Alexander GJ (2005) Compromised lymphocytes infiltrate hepatocellular carcinoma: the role of T-regulatory cells. Hepatology 41:722–730

    Article  PubMed  CAS  Google Scholar 

  • Wada Y, Nakashima O, Kutami R, Yamamoto O, Kojiro M (1998) Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration. Hepatology 27:407–414

    Article  PubMed  CAS  Google Scholar 

  • Wong YQ, Qiu SJ, Tang ZY, Ye SL, Liu YK, Fan J, Sun RX, Zhao Y (2005) Changes of immune function of dendritic cell (DC) derived from HBV-related hepatocellualr carcinoma (HCC) patients’ peripheral blood monocytes (PBMC) pulsed with tumor antigen (Chin). Zhonghua Gan Zang Bing Za Zhi 13:339–342

    PubMed  Google Scholar 

  • Yin X, Lu M, Liang L, Lai Y, Huang J, Li Z (2002) Infiltration of dendritic cells and lymphocytes in hepatocellular carcinoma tissue (Chin). Zhonghua Wai Ke Za Zhi 40:336–338

    PubMed  Google Scholar 

  • Yin XY, Lu MD, Lai YR, Liang LJ, Huang JF (2003) Prognostic significances of tumor-infiltrating S-100 positive dendritic cells and lymphocytes in patients with hepatocellular carcinoma. Hepatogastroenterology 50:1281–1284

    PubMed  Google Scholar 

  • Yu P, Lee Y, Liu W, Krausz T, Chong A, Schreiber H, Fu YX (2005) Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med 201:779–791

    Article  PubMed  CAS  Google Scholar 

  • Zeid NA, Muller HK (1993) S100 positive dendritic cells in human lung tumors associated with cell differentiation and enhanced survival. Pathology 25:338–343

    Article  PubMed  CAS  Google Scholar 

  • Zhang G, Ni XH (1998) The double immunohistochemical staining with double enzyme renovated by microwave (Chin). Zhejiang Tumor 4:63

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the National Natural Science Foundation of China (No. 30200268).

Author information

Author notes

  1. Xiao-Yan Cai

    Present address: Department of General Surgery, Gongli Hospital of Shanghai, 207 Ju Ye Road, 200135, Shanghai, People’s Republic of China

Authors and Affiliations

  1. Liver Cancer Institute and Zhong Shan Hospital, Fudan University, 136 Yi Xue Yuan Road, 200032, Shanghai, People’s Republic of China

    Xiao-Yan Cai, Qiang Gao, Shuang-Jian Qiu, Sheng-Long Ye, Zhi-Quan Wu, Jia Fan & Zhao-You Tang

Authors
  1. Xiao-Yan Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shuang-Jian Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sheng-Long Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhi-Quan Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jia Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhao-You Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shuang-Jian Qiu.

Additional information

Xiao-Yan Cai and Qiang Gao contributed equally to this paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cai, XY., Gao, Q., Qiu, SJ. et al. Dendritic cell infiltration and prognosis of human hepatocellular carcinoma. J Cancer Res Clin Oncol 132, 293–301 (2006). https://doi.org/10.1007/s00432-006-0075-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-006-0075-y

Keywords

Search

Navigation