Regulatory T cells control toxicity in a humanized model of IL-2 therapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29176694.
- Also identified by DOI 10.1038/s41467-017-01570-9 and PMC identifier 5701141.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
While patient selection and clinical management have reduced high-dose IL-2 (HDIL2) immunotherapy toxicities, the immune mechanisms that underlie HDIL2-induced morbidity remain unclear. Here we show that dose-dependent morbidity and mortality of IL-2 immunotherapy can be modeled in human immune system (HIS) mice. Depletion of human T cell subsets during the HDIL2 treatment reduces toxicity, pointing to the central function of T cells. Preferential expansion of effector T cells secondary to defective suppressive capacity of regulatory T (T<sub>reg</sub>) cells after HDIL2 therapy further underscores the importance of T<sub>reg</sub> in the maintenance of immune tolerance. IL-2 toxicity is induced by selective depletion or inhibition of T<sub>reg</sub> after LDIL2 therapy, and is ameliorated in HDIL2-treated HIS mice receiving the PIM-1 kinase inhibitor, Kaempferol. Modeling IL-2 pathophysiology in HIS mice offers a means to understand the functions of effector and regulatory T cells in immune-mediated toxicities associated with cancer immunotherapy.
Medical subject headings
- Interleukin-2
- Neoplasms
- T-Lymphocytes, Regulatory