title: IL-15 enhances the antitumor effect of human antigen-specific CD8+T cells by cellular senescence delay.
abstract: Optimal expansion protocols for adoptive human T-cell therapy often include interleukin (IL)-15; however, the mechanism by which IL-15 improves thein vivoantitumor 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 growthin 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.
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Center Laboratory, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Weng
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Kelsey E
authors.initials: KE
authors.lastname: Moriarty
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Flavio Egidio
authors.initials: FE
authors.lastname: Baio
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Fuliang
authors.initials: F
authors.lastname: Chu
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Sung-Doo
authors.initials: SD
authors.lastname: Kim
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Zuliang
authors.initials: Z
authors.lastname: Jie
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Wencai
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yi
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Sattva S
authors.initials: SS
authors.lastname: Neelapu
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
keywords: IL-15; Idiotype; T cells; immunotherapy; myeloma; senescence