Journal of Hepatology
Volume 52, Issue 3 , Pages 370-379 , March 2010

Inflammatory tumour microenvironment is associated with superior survival in hepatocellular carcinoma patients

  • Valerie Chew

      Affiliations

    • Singapore Immunology Network, (SIgN), Agency for Science, Technology and Research (A∗STAR), Biopolis, Immunos #04-00, 8A Biomedical Grove, Singapore 138648, Singapore
    • ,
  • Charlene Tow

      Affiliations

    • Singapore Immunology Network, (SIgN), Agency for Science, Technology and Research (A∗STAR), Biopolis, Immunos #04-00, 8A Biomedical Grove, Singapore 138648, Singapore
    • ,
  • Marissa Teo

      Affiliations

    • National Cancer Centre, Singapore
    • ,
  • Hing Lok Wong

      Affiliations

    • Singapore Immunology Network, (SIgN), Agency for Science, Technology and Research (A∗STAR), Biopolis, Immunos #04-00, 8A Biomedical Grove, Singapore 138648, Singapore
    • ,
  • Jasmine Chan

      Affiliations

    • Singapore Immunology Network, (SIgN), Agency for Science, Technology and Research (A∗STAR), Biopolis, Immunos #04-00, 8A Biomedical Grove, Singapore 138648, Singapore
    • ,
  • Adam Gehring

      Affiliations

    • Singapore Institute for Clinical Sciences (SICS), BMSI, A∗STAR, Singapore
    • ,
  • Marie Loh

      Affiliations

    • Cancer Science Institute of Singapore (CSI Singapore), National University of Singapore (NUS), Singapore
    • ,
  • Alexandre Bolze

      Affiliations

    • Singapore Immunology Network, (SIgN), Agency for Science, Technology and Research (A∗STAR), Biopolis, Immunos #04-00, 8A Biomedical Grove, Singapore 138648, Singapore
    • ,
  • Richard Quek

      Affiliations

    • National Cancer Centre, Singapore
    • ,
  • Victor K.M. Lee

      Affiliations

    • Department of Pathology, National University Hospital, Singapore
    • ,
  • Kang Hoe Lee

      Affiliations

    • Asian Centre for Liver Diseases and Transplantation, Gleneagles Hospital, Singapore
    • ,
  • Jean-Pierre Abastado

      Affiliations

    • Singapore Immunology Network, (SIgN), Agency for Science, Technology and Research (A∗STAR), Biopolis, Immunos #04-00, 8A Biomedical Grove, Singapore 138648, Singapore
    • ,
  • Han Chong Toh

      Affiliations

    • National Cancer Centre, Singapore
    • These authors contributed equally to this work.
    • ,
  • Alessandra Nardin

      Affiliations

    • Singapore Immunology Network, (SIgN), Agency for Science, Technology and Research (A∗STAR), Biopolis, Immunos #04-00, 8A Biomedical Grove, Singapore 138648, Singapore
    • Corresponding Author InformationCorresponding author. Tel.: +65 64070033; fax: +65 64642057.
    • These authors contributed equally to this work.

Received 7 May 2009 ,Revised 3 July 2009 ,Accepted 14 July 2009.

References 

  1. Tobe T, Uchino J, Endo Y, Oto M, Okamoto E, Kojiro M, et al. Predictive factors for long term prognosis after partial hepatectomy for patients with hepatocellular carcinoma in Japan. The Liver Cancer Study Group of Japan. Cancer. 1994;74:2772–2780
  2. Kremsdorf D, Soussan P, Paterlini-Brechot P, Brechot C. Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis. Oncogene. 2006;25:3823–3833
  3. Nakamoto Y, Guidotti LG, Kuhlen CV, Fowler P, Chisari FV. Immune pathogenesis of hepatocellular carcinoma. J Exp Med. 1998;188:341–350
  4. Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 2007;317:121–124
  5. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow?. Lancet. 2001;357:539–545
  6. de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6:24–37
  7. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumours predict clinical outcome. Science. 2006;313:1960–1964
  8. Dieu-Nosjean MC, Antoine M, Danel C, Heudes D, Wislez M, Poulot V, et al. Long-term survival for patients with non-small-cell lung cancer with intratumoural lymphoid structures. J Clin Oncol. 2008;26:4410–4417
  9. Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med. 2008;14:518–527
  10. Gao Q, Qiu SJ, Fan J, Zhou J, Wang XY, Xiao YS, et al. Intratumoural balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J Clin Oncol. 2007;25:2586–2593
  11. Wada Y, Nakashima O, Kutami R, Yamamoto O, Kojiro M. Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration. Hepatology. 1998;27:407–414
  12. Budhu A, Forgues M, Ye QH, Jia HL, He P, Zanetti KA, et al. Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell. 2006;10:99–111
  13. Lee JS, Chu IS, Heo J, Calvisi DF, Sun Z, Roskams T, et al. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology. 2004;40:667–676
  14. Ye QH, Qin LX, Forgues M, He P, Kim JW, Peng AC, et al. Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med. 2003;9:416–423
  15. Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol. 2000;132:365–386
  16. Cronin M, Pho M, Dutta D, Stephans JC, Shak S, Kiefer MC, et al. Measurement of gene expression in archival paraffin-embedded tissues: development and performance of a 92-gene reverse transcriptase-polymerase chain reaction assay. Am J Pathol. 2004;164:35–42
  17. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Stor. 1995;57:289–300
  18. Miyake K. Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol. 2007;19:3–10
  19. Cavassani KA, Ishii M, Wen H, Schaller MA, Lincoln PM, Lukacs NW, et al. TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events. J Exp Med. 2008;205:2609–2621
  20. Lewis CE, Pollard JW. Distinct role of macrophages in different tumour microenvironments. Cancer Res. 2006;66:605–612
  21. Nardin A, Abastado JP. Macrophages and cancer. Front Biosci. 2008;13:3494–3505
  22. Pisegna S, Pirozzi G, Piccoli M, Frati L, Santoni A, Palmieri G. P38 MAPK activation controls the TLR3-mediated up-regulation of cytotoxicity and cytokine production in human NK cells. Blood. 2004;104:4157–4164
  23. Schmidt KN, Leung B, Kwong M, Zarember KA, Satyal S, Navas TA, et al. APC-independent activation of NK cells by the Toll-like receptor 3 agonist double-stranded RNA. J Immunol. 2004;172:138–143
  24. Tabiasco J, Devevre E, Rufer N, Salaun B, Cerottini JC, Speiser D, et al. Human effector CD8+ T lymphocytes express TLR3 as a functional coreceptor. J Immunol. 2006;177:8708–8713
  25. Tu Z, Bozorgzadeh A, Pierce RH, Kurtis J, Crispe IN, Orloff MS. TLR-dependent cross talk between human Kupffer cells and NK cells. J Exp Med. 2008;205:233–244
  26. Polentarutti N, Allavena P, Bianchi G, Giardina G, Basile A, Sozzani S. Et al. IL-2-regulated expression of the monocyte chemotactic protein-1 receptor (CCR2) in human NK cells: characterization of a predominant 3.4-kilobase transcript containing CCR2B and CCR2A sequences. J Immunol. 1997;158:2689–2694
  27. Sato W, Aranami T, Yamamura T. Cutting edge: human Th17 cells are identified as bearing CCR2+CCR5− phenotype. J Immunol. 2007;178:7525–7529
  28. Lang KS, Georgiev P, Recher M, Navarini AA, Bergthaler A, Heikenwalder M, et al. Immunoprivileged status of the liver is controlled by Toll-like receptor 3 signaling. J Clin Invest. 2006;116:2456–2463
  29. Doherty DG, O’Farrelly C. Innate and adaptive lymphoid cells in the human liver. Immunol Rev. 2000;174:5–20
  30. Chen Y, Wei H, Gao B, Hu Z, Zheng S, Tian Z. Activation and function of hepatic NK cells in hepatitis B infection: an underinvestigated innate immune response. J Viral Hepat. 2005;12:38–45
  31. Irshad M, Khushboo I, Singh S, Singh S. Hepatitis C virus (HCV): a review of immunological aspects. Int Rev Immunol. 2008;27:497–517
  32. Winnock M, Garcia-Barcina M, Huet S, Bernard P, Saric J, Bioulac-Sage P, et al. Functional characterization of liver-associated lymphocytes in patients with liver metastasis. Gastroenterology. 1993;105:1152–1158
  33. Hoshida Y, Villanueva A, Kobayashi M, Peix J, Chiang DY, Camargo A, et al. Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med. 2008;359:1995–2004

PII: S0168-8278(09)00475-9

doi: 10.1016/j.jhep.2009.07.013

Journal of Hepatology
Volume 52, Issue 3 , Pages 370-379 , March 2010

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