PEGylated IL-10 (Pegilodecakin) Induces Systemic Immune Activation, CD8⁺ T Cell Invigoration and Polyclonal T Cell Expansion in Cancer Patients

Tumor-reactive T cell exhaustion prevents the success of immune therapies. Pegilodecakin activates intratumoral CD8⁺ T cells in mice and induces objective tumor responses in patients. Here we report that pegilodecakin induces hallmarks of CD8⁺ T cell immunity in cancer patients, including elevation of interferon-γ and GranzymeB, expansion and activation of intratumoral CD8⁺ T cells, and proliferation and expansion of LAG-3⁺ PD-1⁺ CD8⁺ T cells. On pegilodecakin, newly expanded T cell clones, undetectable at baseline, become 1%–10% of the total T cell repertoire in the blood. Elevation of interleukin-18, expansion of LAG-3⁺ PD-1⁺ T cells and novel T cell clones each correlated with objective tumor responses. Combined pegilodecakin with anti-PD-1 increased the expansion of LAG-3⁺ PD-1⁺ CD8⁺ T cells. Naing et al. report that pegilodecakin, PEGylated IL-10, which achieves objective tumor responses in patients, induces hallmarks of CD8⁺ T cell immunity in cancer patients. Pegilodecakin promotes expansion of underrepresented T cell clones as well as LAG-3⁺ PD-1⁺ CD8⁺ T cells, which are further induced by anti-PD-1.