7.1.5　Interleukin-10

IL-10 is released by innate and adaptive immune cells to fine-tune the activity of pro-inflammatory cytokines.IL-10 is considered an immunosuppressive cytokine as it can decrease the antigen presenting activity of DCs and inhibit the cytotoxic and cytokine release functions performed by T and NK lymphocytes.However, recent reports point to a context-dependent outcome of IL-10 activity.In chronic infections and cancer, autocrine IL-10 activity on CD8+T lymphocytes has been shown to be crucial for inhibiting antigen-induced CD8+ T cell apoptosis, thereby prolonging the effector activity of these cytotoxic lymphocytes.This concept has been evaluated in a phase I clinical trial in advanced, treatment-refractory tumors (NCT02009449) using IL-10 conjugated with PEG to increase its half-life.Administration of the PEGylated cytokine (termed pegilodecakin) is well tolerated, and grade 3-4 immune-related adverse effects were detected in only 15% of patients.Partial responses were observed in patients with uveal melanoma, RCC and colorectal cancer.In 2018, it was reported that the combination of pegilodecakin with nivolumab or pembrolizumab was tolerable in 38 patients with RCC.The clinical activity of pegilodecakin looks promising, with 50%of patients achieving a RECIST 1.1 response, 9% of which were complete.(https://www.daowen.com)