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Cancer Immunol Immunother. 2012 Nov;61(11):2183-92. doi: 10.1007/s00262-012-1277-6. Epub 2012 May 22.

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

Author information

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.

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.

PMID:
22729557
DOI:
10.1007/s00262-012-1277-6
[Indexed for MEDLINE]

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