IL-6-mediated environmental conditioning of defective Th1 differentiation dampens antitumour immune responses in old age

Hirotake Tsukamoto (), Satoru Senju, Keiko Matsumura, Susan L. Swain and Yasuharu Nishimura ()
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Hirotake Tsukamoto: Graduate School of Medical Sciences, Kumamoto University
Satoru Senju: Graduate School of Medical Sciences, Kumamoto University
Keiko Matsumura: Graduate School of Medical Sciences, Kumamoto University
Susan L. Swain: University of Massachusetts Medical School
Yasuharu Nishimura: Graduate School of Medical Sciences, Kumamoto University

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: Abstract Decline in immune function and inflammation concomitantly develop with ageing. Here we focus on the impact of this inflammatory environment on T cells, and demonstrate that in contrast to successful tumour elimination in young mice, replenishment of tumour-specific CD4+ T cells fails to induce tumour regression in aged hosts. The impaired antitumour effect of CD4+ T cells with their defective Th1 differentiation in an aged environment is restored by interleukin (IL)-6 blockade or IL-6 deficiency. IL-6 blockade also restores the impaired ability of CD4+ T cells to promote CD8+ T-cell-dependent tumour elimination in aged mice, which requires IFN-γ. Furthermore, IL-6-stimulated production of IL-4/IL-21 through c-Maf induction is responsible for impaired Th1 differentiation. IL-6 also contributes to IL-10 production from CD4+ T cells in aged mice, causing attenuated responses of CD8+ T cells. These findings suggest that IL-6 serves as an extrinsic factor counteracting CD4+ T-cell-mediated immunity against tumour in old age.

Date: 2015
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DOI: 10.1038/ncomms7702

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