Title |
IL-15 enhances the antitumor effect of human antigen-specific CD8+ T cells by cellular senescence delay
|
---|---|
Published in |
OncoImmunology, October 2016
|
DOI | 10.1080/2162402x.2016.1237327 |
Pubmed ID | |
Authors |
Jinsheng Weng, Kelsey E. Moriarty, Flavio Egidio Baio, Fuliang Chu, Sung-Doo Kim, Jin He, Zuliang Jie, Xiaoping Xie, Wencai Ma, Jianfei Qian, Liang Zhang, Jing Yang, Qing Yi, Sattva S. Neelapu, Larry W. Kwak |
Abstract |
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 P21(WAF1), P16(INK4a), 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 50% |
Unknown | 3 | 50% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Practitioners (doctors, other healthcare professionals) | 2 | 33% |
Scientists | 2 | 33% |
Members of the public | 2 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 27 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 7 | 26% |
Researcher | 5 | 19% |
Student > Doctoral Student | 3 | 11% |
Student > Bachelor | 2 | 7% |
Other | 2 | 7% |
Other | 2 | 7% |
Unknown | 6 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 8 | 30% |
Biochemistry, Genetics and Molecular Biology | 5 | 19% |
Medicine and Dentistry | 4 | 15% |
Agricultural and Biological Sciences | 3 | 11% |
Unknown | 7 | 26% |