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Naïve CD8 + T cell derived tumor-specific cytotoxic effectors as a potential remedy for overcoming TGF-β immunosuppression in the tumor microenvironment

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Title
Naïve CD8 + T cell derived tumor-specific cytotoxic effectors as a potential remedy for overcoming TGF-β immunosuppression in the tumor microenvironment
Author(s)
Nguyen H.H.; Kim T.; Song S.Y.; Park S.; Cho H.H.; Jung S.-H.; Ahn J.-S.; Kim H.-J.; Lee J.-J.; Hee-Ok Kim; Jae-Ho Cho; Yang D.-H.
Publication Date
2016-06
Journal
SCIENTIFIC REPORTS, v.6, no., pp.28208 -
Publisher
NATURE PUBLISHING GROUP
Abstract
Despite of the potential implications for cancer immunotherapy, conventional approaches using in vitro expanded CD8 + T cells have suboptimal outcomes, mostly due to loss of functionality from cellular exhaustion. We therefore investigated the phenotypic and functional differences among in vitro activated CD8 + T cells of three different sources, namely naïve (NT eff), memory (MT eff) and tumor-infiltrating lymphocytes (TIL eff) from human and mice, to better understand mechanisms behind potent effector functions and potential for overcoming current limitations. In line with the greater proliferation activity and longer telomere lengths of NT eff populations, cells of naïve origin exhibited significantly less amounts of T cell exhaustion markers than those of MT eff and TIL eff, and moreover, acquired distinct expression patterns of memory-promoting transcription factors, T-bet and Eomes, induced in a rapid and sustainable manner. NT eff cells appeared to have lower expression of Foxp1 and were refractory to apoptosis upon TGF-β conditioning, implying better survival potential and resistance to tumor-induced immune suppression. Of CD8 + T cell pools activated to tumor-specific CTLs, naïve cell generated effectors possessed the most potent cytotoxic activity, validating implications for use in rational design of adoptive immunotherapy
URI
http://pr.ibs.re.kr/handle/8788114/2821
DOI
10.1038/srep28208
ISSN
2045-2322
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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