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. [Display omitted] •Pegilodecakin induces systemic and intratumoral CD8+ T cell activation in patients•PD-1+ Lag3+ CD8+ T cells and previously undetected T cell clones are expanded•IFN-γ, IL-18, GranzymeB, and FasL are elevated across tumor types•The magnitude of systemic immune activation correlates with tumor response 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.