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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-09

AUTHORS

Hong Hanh Nguyen, Therasa Kim, Sang Yun Song, Somang Park, Hyang Hee Cho, Sung-Hoon Jung, Jae-Sook Ahn, Hyeoung-Joon Kim, Je-Jung Lee, Hee-Ok Kim, Jae-Ho Cho, Deok-Hwan Yang

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 (NTeff), memory (MTeff) and tumor-infiltrating lymphocytes (TILeff) 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 NTeff populations, cells of naïve origin exhibited significantly less amounts of T cell exhaustion markers than those of MTeff and TILeff, and moreover, acquired distinct expression patterns of memory-promoting transcription factors, T-bet and Eomes, induced in a rapid and sustainable manner. NTeff 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. More... »

PAGES

28208

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep28208

DOI

http://dx.doi.org/10.1038/srep28208

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1006741507

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27306834


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