IL-15 enhances the antitumor effect of human antigen-specific CD8+ T cells by cellular senescence delay
| Autor: | Jing Yang, Qing Yi, Sung-Doo Kim, Jinsheng Weng, Zuliang Jie, Kelsey E. Moriarty, Wencai Ma, Xiaoping Xie, Jianfei Qian, Liang Zhang, Larry W. Kwak, Fuliang Chu, Sattva S. Neelapu, Flavio Egidio Baio, Jin He |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Idiotype Adoptive cell transfer medicine.medical_treatment Immunology Immunotherapy Biology Molecular biology Epitope Cell biology 03 medical and health sciences Interleukin 21 030104 developmental biology Oncology Interleukin 15 medicine Immunology and Allergy Cytotoxic T cell CD8 Original Research |
| Popis: | Optimal expansion protocols for adoptive human T-cell therapy often include interleukin (IL)-15; however, the mechanism by which IL-15 improves the in vivo 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 in vivo, 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 P21WAF1, P16INK4a, 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. |
| Databáze: | OpenAIRE |
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