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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 IFN? 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 IFN? 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.

SUBMITTER: Oft M

PROVIDER: S-EPMC7129358 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Oft Martin M

Seminars in immunology 20190801

The expansion and activation of tumor antigen reactive CD8<sup>+</sup> 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<sup>+</sup> T cells, leading to spontaneous tumor development in IL-10 deficient patients and m ...[more]

PMID: 31706853

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