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Higher numbers of T-bet+ intratumoral lymphoid cells correlate with better survival in gastric cancer

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Abstract

In the present study, we studied the expression of T-bet, a key marker for type 1 immune responses, within the tumor microenvironment of gastric cancer, and analyzed its association with clinicopathological parameters. One hundred and fifty-two archival paraffin-embedded gastric tumor tissues were collected, and the expression of T-bet in these cancer tissue specimens was examined by immunohistochemistry. T-bet+ tumor-infiltrating lymphocytes (TILs) in some gastric cancer tissues were further characterized by flow cytometric analysis. The density of T-bet+ TILs in gastric cancer tissues in relation to patient’s clinicopathological parameters and postoperative prognosis has been analyzed. Herein, we have found significant increases in T-bet+ lymphocytes in tumor tissues as compared with normal stomach tissues, gastritis tissues or gastric polyp specimens. T-bet+ cells mainly consisted of CD4+, CD8+ and CD56+ TILs. In addition, lower numbers of T-bet+ TILs were associated with poor clinicopathological parameters such as invasion to muscular layer, larger tumor size and advanced cancer stages. Moreover, patients with higher numbers of T-bet+ TILs have longer disease-free survival and overall survival. Thus, our study supports the idea that tumor growth elicits spontaneous type 1 cellular immune responses and tumor progression is associated with suppression of antitumor immunity. T-bet expression within tumor can serve as a prognostic indicator for gastric cancer and a potential biomarker for immunotherapy.

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References

  1. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60(5):277–300

    Article  PubMed  Google Scholar 

  2. Gajewski TF, Meng Y, Harlin H (2006) Immune suppression in the tumor microenvironment. J Immunother 29(3):233–240

    Article  PubMed  CAS  Google Scholar 

  3. Finn OJ (2008) Cancer immunology. N Engl J Med 358(25):2704–2715

    Article  PubMed  CAS  Google Scholar 

  4. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313(5795):1960–1964

    Article  PubMed  CAS  Google Scholar 

  5. Glimcher LH (2007) Trawling for treasure: tales of T-bet. Nat Immunol 8(5):448–450

    Article  PubMed  CAS  Google Scholar 

  6. Werneck MB, Lugo-Villarino G, Hwang ES, Cantor H, Glimcher LH (2008) T-bet plays a key role in NK-mediated control of melanoma metastatic disease. J Immunol 180(12):8004–8010

    PubMed  CAS  Google Scholar 

  7. Garrett WS, Punit S, Gallini CA, Michaud M, Zhang D, Sigrist KS, Lord GM, Glickman JN, Glimcher LH (2009) Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells. Cancer Cell 16(3):208–219

    Article  PubMed  CAS  Google Scholar 

  8. Lipscomb MW, Chen L, Taylor JL, Goldbach C, Watkins SC, Kalinski P, Butterfield LH, Wesa AK, Storkus WJ (2009) Ectopic T-bet expression licenses dendritic cells for IL-12-independent priming of type 1 T cells in vitro. J Immunol 183(11):7250–7258

    Article  PubMed  CAS  Google Scholar 

  9. Qu Y, Chen L, Pardee AD, Taylor JL, Wesa AK, Storkus WJ (2010) Intralesional delivery of dendritic cells engineered to express T-bet promotes protective type 1 immunity and the normalization of the tumor microenvironment. J Immunol 185(5):2895–2902

    Article  PubMed  CAS  Google Scholar 

  10. Zhu Y, Ju S, Chen E, Dai S, Li C, Morel P, Liu L, Zhang X, Lu B (2010) T-bet and Eomesodermin are required for T cell-mediated antitumor immune responses. J Immunol 185(6):3174–3183

    Article  PubMed  CAS  Google Scholar 

  11. Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Galon J (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353(25):2654–2666

    Article  PubMed  CAS  Google Scholar 

  12. LH S, C W (2002) TNM Classification of Malignant Tumours (6th edited). UICC (International Union Against Cancer): 65–68

  13. Chen LJ, Sun J, Wu HY, Zhou SM, Tan Y, Tan M, Shan BE, Lu BF, Zhang XG (2011) B7–H4 expression associates with cancer progression and predicts patient’s survival in human esophageal squamous cell carcinoma. Cancer Immunol Immunother 60(7):1047–1055

    Article  PubMed  CAS  Google Scholar 

  14. Sun J, Chen L, Zhang G, Jiang J, Zhu M, Tan Y, Wang H, Lu B, Zhang X (2010) Clinical significance and regulation of the costimulatory molecule B7–H3 in human colorectal carcinoma. Cancer Immunol Immunother 59(8):1163–1171

    Article  PubMed  CAS  Google Scholar 

  15. Peng SL, Townsend MJ, Hecht JL, White IA, Glimcher LH (2004) T-bet regulates metastasis rate in a murine model of primary prostate cancer. Cancer Res 64(2):452–455

    Article  PubMed  CAS  Google Scholar 

  16. Stoicov C, Fan X, Liu JH, Bowen G, Whary M, Kurt-Jones E, Houghton J (2009) T-bet knockout prevents Helicobacter felis-induced gastric cancer. J Immunol 183(1):642–649

    Article  PubMed  CAS  Google Scholar 

  17. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH (2000) A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100(6):655–669

    Article  PubMed  CAS  Google Scholar 

  18. Mullen AC, High FA, Hutchins AS, Lee HW, Villarino AV, Livingston DM, Kung AL, Cereb N, Yao TP, Yang SY, Reiner SL (2001) Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 292(5523):1907–1910

    Article  PubMed  CAS  Google Scholar 

  19. Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331(6024):1565–1570

    Article  PubMed  CAS  Google Scholar 

  20. Iida T, Iwahashi M, Katsuda M, Ishida K, Nakamori M, Nakamura M, Naka T, Ojima T, Ueda K, Hayata K, Nakamura Y, Yamaue H (2011) Tumor-infiltrating CD4 + Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer. Oncol Rep 25(5):1271–1277

    PubMed  CAS  Google Scholar 

  21. De Monte L, Reni M, Tassi E, Clavenna D, Papa I, Recalde H, Braga M, Di Carlo V, Doglioni C, Protti MP (2011) Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J Exp Med 208(3):469–478

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank senior pathologists Chang-qing Lu, Wei Zhao, Jun Xie and Yuan-dong Chen (Department of Pathology, The Third Affiliated Hospital of Soochow University, Jiangsu Changzhou, China) for their expert suggestions and technical assistances. This work was supported in part by grants from the National Natural Science Foundation of China (No. 81171653, 31170866, 30950022 and 30972703), Jiangsu Province Science and Technology Innovation Fund (2012-85), and the Innovative Talents Training Project of Changzhou Health Bureau.

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The authors declare that they have no competing interests to this paper.

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Correspondence to Bin-feng Lu or Jing-ting Jiang.

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L. Chen and X. Zheng contributed equally to this work.

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Chen, Lj., Zheng, X., Shen, Yp. et al. Higher numbers of T-bet+ intratumoral lymphoid cells correlate with better survival in gastric cancer. Cancer Immunol Immunother 62, 553–561 (2013). https://doi.org/10.1007/s00262-012-1358-6

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  • DOI: https://doi.org/10.1007/s00262-012-1358-6

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