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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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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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