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Th9 cells promote antitumor immunity via IL-9 and IL-21 and demonstrate atypical cytokine expression in breast cancer.

Th9 cells promote antitumor immunity via IL-9 and IL-21 and demonstrate atypical cytokine expression in breast cancer.
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You FP, Zhang J, Cui T, Zhu R, Lv CQ, Tang HT, Sun DW,


You FP, Zhang J, Cui T, Zhu R, Lv CQ, Tang HT, Sun DW, (click to view)

You FP, Zhang J, Cui T, Zhu R, Lv CQ, Tang HT, Sun DW,

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International immunopharmacology 2017 09 1552() 163-167 pii 10.1016/j.intimp.2017.08.031

Abstract

Breast cancer is a major cause of cancer-related death in women. Antitumor T cell responses play critical therapeutic roles, including direct cytotoxicity mediated by CD8(+) T cells and immunomodulatory roles mediated by CD4(+) T cells. The IL-9-expressing Th9 cells are recently found to present antitumor immunity in melanoma and lung adenocarcinoma. In this study, we found that IL-9 expression in the serum and in circulating CD4(+) T cells were significantly upregulated in breast cancer patients compared to healthy controls. The IL-9-expressing Th9 cells were enriched in the CCR4(-)CCR6(-)CXCR3(-) subset. Upon TCR stimulation, this subset also presented potent IL-10 and IL-21 expression in addition to IL-9 expression. CCR4(-)CCR6(-)CXCR3(-) CD4(+) T cells also assisted in the killing of autologous tumor cells by CD8(+) T cells, but did not initiate cytotoxicity by themselves. This enhancement in CD8(+) T cell-mediated cytotoxicity was dependent on IL-9 as well as on IL-21. Interestingly, the tumor-infiltrating Th9 cells presented comparable IL-9, reduced IL-10, and elevated IL-21 expression compared with their counterparts in the peripheral blood. Together, these results demonstrated that IL-9-expressing Th9 cells were upregulated in breast cancer patients and potentially possessed antitumor roles by enhancing CD8(+) T cell-mediated cytotoxicity.

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