Interleukin-7 protects CD8 ⁺ T cells from adenosine-mediated immunosuppression

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.

Ecto-5′-Nucleotidase (CD73) Regulates the Survival of CD8+ T Cells

“…This observation agrees with our previous evidence demonstrating a crosstalk between adenosine and IL-7 signaling, where adenosine has been shown to induce CD127 expression through A2A receptor signaling (Cekic et al, 2013). Moreover, our recent findings indicate that IL-7 signaling has been shown to support CD8+ T cell maintenance despite the presence of extracellular adenosine (Koyas et al, 2021). Thus, it is possible to speculate that the decreased frequency of CD73KO cells under homeostatic conditions may be explained by defective A2AR signaling that translates into a reduced CD127 expression and weak IL-7 signaling for the maintenance of these cells.…”

Interleukin-7 regulates CD127 expression and promotes CD8+ T cell activity in patients with primary cutaneous melanoma

“…IL-7 signaling pathway influence anti-TNF responsiveness and T cell gut homing in inflammatory bowel disease [ 43 ]. Transcription factor FoxO1, which ameliorated TNF-α-induced tissue damage [ 46 ], also served as the downstream of IL-7 signaling pathway and contributed to adenosine-mediated CD8 + T cells immunosuppression [ 47 ]. Thus, there might be another signaling pathway, which was activated by IL-7, leading to TNF-α production.…”

Assessment of Fatigue and Recovery in Sport: Narrative Review

“…Adenosine concentration increases during exercise and its concentration affects blood flow in skeletal muscles [109], plus has profound tissue-protective effects in situations of ischemia and inflammation [110]. Adenosine inhibits CD8 + T cells by activating adenosine receptors and can cause a significant immunosuppression [111]. It is a promising marker for training adaptations not associated with muscle mass [112].…”