European Journal of Surgical Oncology
Volume 34, Issue 2 , Pages 173-179 , February 2008

Prognostic value of tumor-infiltrating FOXP3+ regulatory T cells in patients with hepatocellular carcinoma

  • A. Sasaki

      Affiliations

    • Department of Surgery, National Hospital Organization Miyazaki Hospital, 19403-4 Kawaminami-machi, Miyazaki 889-1301, Japan
    • Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan
    • Department of Surgery I, Oita University Faculty of Medicine, 1-1 Yufu 889-5593, Japan
    • Corresponding Author InformationCorresponding author. Department of Surgery, National Hospital Organization Miyazaki Hospital, 19403-4 Kawaminami-machi, Miyazaki 889-1301, Japan. Tel.: +81 983 27 1036; fax: +81 983 27 5033.
    • ,
  • F. Tanaka

      Affiliations

    • Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan
    • ,
  • K. Mimori

      Affiliations

    • Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan
    • ,
  • H. Inoue

      Affiliations

    • Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan
    • ,
  • S. Kai

      Affiliations

    • Department of Surgery I, Oita University Faculty of Medicine, 1-1 Yufu 889-5593, Japan
    • ,
  • K. Shibata

      Affiliations

    • Department of Surgery I, Oita University Faculty of Medicine, 1-1 Yufu 889-5593, Japan
    • ,
  • M. Ohta

      Affiliations

    • Department of Surgery I, Oita University Faculty of Medicine, 1-1 Yufu 889-5593, Japan
    • ,
  • S. Kitano

      Affiliations

    • Department of Surgery I, Oita University Faculty of Medicine, 1-1 Yufu 889-5593, Japan
    • ,
  • M. Mori

      Affiliations

    • Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan

,Accepted 21 August 2007.

References 

  1. Sasaki A, Iwashita Y, Shibata K, Matsumoto T, Ohta M, Kitano S. Improved long-term survival after liver resection for hepatocellular carcinoma in the modern era: a retrospective study from HCV-endemic areas. World J Surg. 2006;30:1567–1578
  2. Hanazaki K, Kajikawa S, Shimozawa N, et al. Survival and recurrence after hepatic resection of 386 consecutive patients with hepatocellular carcinoma. J Am Coll Surg. 2000;191:381–388
  3. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995;155:1151–1164
  4. Dercamp C, Chemin K, Caux C, Trinchieri G, Vicari AP. Distinct and overlapping roles of interleukin-10 and CD25+ regulatory T cells in the inhibition of antitumor CD8 T-cell responses. Cancer Res. 2005;65:8479–8486
  5. Ghiringhelli F, Menard C, Terme M, et al. CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Med. 2005;202:1075–1085
  6. Curiel T, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10:942–949
  7. Badoual C, Hans S, Rodriguez J, et al. Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res. 2006;12:465–472
  8. Ormandy LA, Hillemann T, Wedemeyer H, Manns MP, Greten TF, Korangy F. Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res. 2005;65:2457–2464
  9. Unitt E, Rushbrook SM, Marshall A, et al. Compromised lymphocytes infiltrate hepatocellular carcinoma: the role of T-regulatory cells. Hepatology. 2005;41:722–730
  10. Yang XH, Yamagiwa S, Ichida T, et al. Increase of CD4+CD25+ regulatory T-cells in the liver of patients with hepatocellular carcinoma. J Hepatol. 2006;45:254–262
  11. Kono K, Kawaida H, Takahashi A, et al. CD4(+)CD25 high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol Immunother. 2006;55:1064–1071
  12. Bueter M, Gasser M, Schramm N, et al. T-cell response to p53 tumor-associated antigen in patients with colorectal carcinoma. Int J Oncol. 2006;28:431–438
  13. Liyanage UK, Moore TT, Joo HG, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol. 2002;169:2756–2761
  14. Hiraoka N, Onozato K, Kosuge T, Hirohashi S. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res. 2006;12:5423–5434
  15. Wald O, Izhar U, Amir G, et al. CD4+ CXCR4 high CD69+ T cells accumulate in lung adenocarcinoma. J Immunol. 2006;177:6983–6990
  16. Ishibashi Y, Tanaka S, Tajima K, Yoshida T, Kuwano H. Expression of Foxp3 in non-small cell lung cancer patients is significantly higher in tumor tissues than in normal tissues, especially in tumors smaller than 30mm. Oncol Rep. 2006;15:1315–1319
  17. Miller AM, Lundberg K, Ozenci V, et al. CD4+ CD25 high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J Immunol. 2006;177:7398–7405
  18. Unitt E, Marshall A, Gelson W, et al. Tumour lymphocytic infiltrate and recurrence of hepatocellular carcinoma following liver transplantation. J Hepatol. 2006;45:246–253
  19. Kobayashi N, Hiraoka N, Yamagami W, et al. FOXP3+ regulatory T cells affect the development and progression of hepatocarcinogenesis. Clin Cancer Res. 2007;13:902–911
  20. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057–1061
  21. Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001;27:20–21
  22. The Liver Cancer Study Group of Japan. General rules for the clinical and pathological study of primary liver cancer. 2nd English ed.. Tokyo: Kanehara & Co., Ltd; 2003;
  23. Wada Y, Nakashima O, Kutami R, Yamamoto O, Kojiro M. Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration. Hepatology. 1998;27:407–414
  24. Diederichsen AC, Hjelmborg JB, Christensen PB, Zeuthen J, Fenger C. Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumour cells. Cancer Immunol Immunother. 2003;52:423–428
  25. Cho Y, Miyamoto M, Kato K, et al. CD4+ and CD8+ T cells cooperate to improve prognosis of patients with esophageal squamous cell carcinoma. Cancer Res. 2003;63:1555–1559
  26. Takahashi T, Kuniyasu Y, Toda M, et al. Immunologic self-tolerance maintained by CD25+ CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol. 1998;10:1969–1980
  27. Sakon M, Umeshita K, Nagano H, et al. Clinical significance of hepatic resection in hepatocellular carcinoma: analysis by disease-free survival curves. Arch Surg. 2000;135:1456–1459
  28. Michel J, Suc B, Montpeyroux F, et al. Liver resection or transplantation for hepatocellular carcinoma? Retrospective analysis of 215 patients with cirrhosis. J Hepatol. 1997;26:1274–1280
  29. Okuda K. Hepatocellular carcinoma: recent progress. Hepatology. 1992;15:948–963
  30. Boettler T, Spangenberg HC, Neumann-Haefelin C, et al. T cell with a CD4+ CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection. J Virol. 2005;79:7860–7867
  31. Stoop JN, van der Molen RG, Baan CC, et al. Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology. 2005;41:771–778

PII: S0748-7983(07)00525-2

doi: 10.1016/j.ejso.2007.08.008

European Journal of Surgical Oncology
Volume 34, Issue 2 , Pages 173-179 , February 2008

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