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

被引：18

作者：

Weng, Jinsheng ^{[1
,2
]}

Moriarty, Kelsey E. ^{[1
]}

Baio, Flavio Egidio ^{[1
]}

Chu, Fuliang ^{[1
]}

Kim, Sung-Doo ^{[1
]}

He, Jin ^{[1
]}

Jie, Zuliang ^{[3
]}

Xie, Xiaoping ^{[3
]}

Ma, Wencai ^{[1
]}

Qian, Jianfei ^{[1
]}

Zhang, Liang ^{[1
]}

Yang, Jing ^{[1
]}

Yi, Qing ^{[1
]}

Neelapu, Sattva S. ^{[1
]}

Kwak, Larry W. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Lymphoma & Myeloma, Houston, TX 77030 USA

[2] Guangzhou Med Univ, Affiliated Hosp 5, Dept Ctr Lab, Guangzhou 510700, Guangdong, Peoples R China

[3] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA

来源：

ONCOIMMUNOLOGY | 2016年 / 5卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Idiotype; IL-15; immunotherapy; myeloma; senescence; T cells; TUMOR-INFILTRATING LYMPHOCYTES; TRIGGERS SENESCENCE; CANCER; EXPANSION; IMMUNOTHERAPY; PATHWAYS; THERAPY; GROWTH; STAT3; DIFFERENTIATION;

D O I：

10.1080/2162402X.2016.1237327

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：12

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