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Increased tumor-infiltrating CD8+Foxp3+ T lymphocytes are associated with tumor progression in human gastric cancer

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Background

CD8+Foxp3+ T lymphocytes have been detected in tumors. However, the distribution, phenotypic features, and regulation of these cells in gastric cancer remain unknown.

Methods

The levels of CD8+Foxp3+ T lymphocytes in the peripheral blood, tumor-draining lymph nodes, non-tumor tissues, and tumor tissues of patients with gastric cancer were detected by flow cytometry. Foxp3 induction in CD8+Foxp3− T cells was investigated in vitro. The suppressive function of CD8+Foxp3+ T lymphocytes was analyzed by their effect on CD4+ T-cell proliferation and IFN-γ production. The percentages of CD8+Foxp3+ T lymphocytes were evaluated for the association with tumor stage.

Results

The frequency of CD8+Foxp3+ T lymphocytes in tumor tissues was significantly higher than that in non-tumor tissues, and similar results were also observed in tumor-draining lymph nodes compared with peripheral blood. Most intratumoral CD8+Foxp3+ T lymphocytes were activated effector cells (CD45RA−CD27−). TGF-β1 levels were positively correlated with the frequency of CD8+Foxp3+ T lymphocytes in tumor tissues, and in vitro TGF-β1 could induce the generation of CD8+Foxp3+ T lymphocytes in a dose-dependent manner. Furthermore, intratumoral CD8+Foxp3+ T lymphocytes suppressed the proliferation and IFN-γ production of CD4+ T cells. Finally, intratumoral CD8+Foxp3+ T lymphocytes were significantly increased with tumor progression in terms of tumor-node-metastasis (TNM) stage.

Conclusions

Our data have shown that increased intratumoral CD8+Foxp3+ T lymphocytes are associated with tumor stage and potentially influence CD4+ T-cell functions, which may provide insights for developing novel immunotherapy protocols against gastric cancer.

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Acknowledgments

This work was supported by grants of the National Natural Science Foundation of China (NSFC, No. 81071412) and National Basic Research Program of China (973 program, No. 2009CB522606). We thank Fang Wang (Analysis and Testing Center) for her help in flow cytometry sorting.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Clinical Microbiology and Immunology, College of Medical Laboratory Science, Third Military Medical University, No. 30 Gaotanyan Street, Chongqing, 400038, People’s Republic of China

    Liu-sheng Peng, Yuan Zhuang, Yun Shi, Ting-ting Wang, Na Chen, Ping Cheng, Tao Liu, Xiao-fei Liu, Jin-yu Zhang, Qian-fei Zuo, Xu-hu Mao, Gang Guo, Dong-shui Lu & Quan-ming Zou

  2. Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, No. 30 Gaotanyan Street, Chongqing, 400038, People’s Republic of China

    Yong-liang Zhao & Pei-wu Yu

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  1. Liu-sheng Peng
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Correspondence to Pei-wu Yu or Quan-ming Zou.

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Liu-sheng Peng and Yuan Zhuang contributed equally to the work.

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Peng, Ls., Zhuang, Y., Shi, Y. et al. Increased tumor-infiltrating CD8+Foxp3+ T lymphocytes are associated with tumor progression in human gastric cancer. Cancer Immunol Immunother 61, 2183–2192 (2012). https://doi.org/10.1007/s00262-012-1277-6

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  • DOI: https://doi.org/10.1007/s00262-012-1277-6

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