Immune regulation and cytotoxic T cell activation of IL-10 agonists - Preclinical and clinical experience

Abstract

The expansion and activation of tumor antigen reactive CD8⁺ T cells are primary goals of immunotherapies for cancer. IL-10 is an anti-inflammatory cytokine with an essential role in the development and proliferation of regulatory T cells, restricting myeloid and chronic inflammatory T cell responses. However, IL-10 is also essential for the expansion of antigen activated, tumor specific CD8⁺ T cells, leading to spontaneous tumor development in IL-10 deficient patients and mice. IL-10 induces IFNγ and cytotoxic mediators in antigen activated T cells. In clinical trials, monotherapy with recombinant, pegylated IL-10 (Pegilodecakin) induced objective responses in cancer patients. Patients receiving pegilodecakin had a systemic increase of IFNγ and granzymes, proliferation and expansion of immune checkpoint positive CD8⁺ T cells. Combination of pegilodecakin with anti-PD-1 appeared to improve on the efficacy of the single agents.

Keywords: CD8 T cell cytotoxicity; Pegylated IL-10; T cell invigoration clinical trial; Tumour immunology.