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Averting antitumor immunity
Within the tumor microenvironment, the nucleoside adenosine accumulates and acts through its cell surface receptors to inhibit the activity of antitumor CD8+ T cells. To alleviate this immunosuppression, therapeutics that target either adenosine production or adenosine receptor signaling are being developed. Koyas et al. showed in mice that the actions of adenosine on tumor-infiltrating CD8+ T cells depended on the milieu within the tumor. In particular, signaling by the cytokine interleukin-7 (IL-7) counteracted the immunosuppressive effects of adenosine, leading to enhanced antitumor immunity in a melanoma model. Together, these findings suggest that targeting IL-7 signaling may alleviate the inhibition of tumor-infiltrating T cells.
Abstract
The nucleoside adenosine accumulates extracellularly in solid tumors and inhibits CD8+ T cells by activating adenosine receptors. The cytokine interleukin-7 (IL-7), which is produced by various tissues and tumors, promotes the survival and maintenance of T cells. Adenosine and IL-7 signaling are being clinically targeted separately or in combination with other therapies for solid tumor indications. Here, we found that IL-7 signaling promoted the accumulation of tumor-associated CD8+ T cells, in part, by preventing adenosine-mediated immunosuppression. Inhibition of the transcription factor FoxO1 downstream of IL-7 receptor signaling was important for protecting CD8+ T cells from suppression by adenosine. These findings have implications for the development of new approaches for cancer immunotherapies that target the adenosine pathway.
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