IL-15 enhances the antitumor effect of human antigen-specific CD8 T cells by cellular senescence delay.

Oncoimmunology 2016 7;5(12):e1237327. Epub 2016 Oct 7.

Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.

Optimal expansion protocols for adoptive human T-cell therapy often include interleukin (IL)-15; however, the mechanism by which IL-15 improves the antitumor effect of T cells remains to be elucidated. Using human T cells generated from HLA-A2+ donors against novel T-cell epitopes derived from the human U266 myeloma cell line Ig light chain V-region (idiotype) as a model, we found that T cells cultured with IL-15 provided superior resistance to tumor growth , compared with IL-2, after adoptive transfer into immunodeficient hosts. This effect of IL-15 was associated with delayed/reversed senescence in tumor antigen-specific memory CD8 T cells mediated through downregulation of P21, P16, and P53 expression. Compared to IL-2, IL-15 stimulation dramatically activated JAK3-STAT5 signaling and inhibited the expression of DNA damage genes. Thus, our study elucidates a new mechanism for IL-15 in the regulation of STAT signaling pathways and CD8 T-cell senescence.

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http://dx.doi.org/10.1080/2162402X.2016.1237327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215241PMC
October 2016
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