1. Interleukin-7 Protects Cd8(+) T Cells From Adenosine-Mediated Immunosuppression
- Author
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Ali Can Savas, Altay Koyas, Suat Tucer, Merve Kayhan, Imran Akdemir, Caglar Cekic, Koyaş, Altay, Tüçer, Suat, Kayhan, Merve, Savaş, Ali Can, Akdemir, İmran, and Çekiç, Çağlar
- Subjects
0303 health sciences ,Chemistry ,medicine.medical_treatment ,Interleukin ,Cell Biology ,Biochemistry ,Adenosine ,Adenosine receptor ,03 medical and health sciences ,0302 clinical medicine ,Cytokine ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Cytotoxic T cell ,Molecular Biology ,Nucleoside ,Transcription factor ,CD8 ,030304 developmental biology ,medicine.drug - 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.
- Published
- 2021