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Cytotoxic T cells isolated from healthy donors and cancer patients kill TGFβ-expressing cancer cells in a TGFβ-dependent manner

引用

Cellular & Molecular Immunology 2021年第2期18卷 415-426页

作者： Morten Orebo Holmström Rasmus Erik johansson Mortensen Angelos Michail Pavlidis Evelina Martinenaite Stine Emilie Weis-Banke mia aaboe-jørgensen Simone Kloch Bendtsen Özcan Met Ayako Wakatsuki Pedersen Marco Donia Inge Marie Svane Mads Hald Andersen Department of Oncology National Center for Cancer Immune TherapyCopenhagen University HospitalHerlevDenmark IO Biotech ApS CopenhagenDenmark Institute for Immunology and Microbiology Copenhagen UniversityCopenhagenDenmark

Transforming growth factor-beta(TGFβ)is a highly potent immunosuppressive *** TGFβis a tumor suppressor in early/premalignant cancer lesions,the cytokine has several tumor-promoting effects in advanced cancer;abrogation of the antitumor immune response is one of the most important tumor-promoting *** several immunoregulatory mechanisms have recently been shown to be targets of specific T cells,we hypothesized that TGFβis targeted by naturally occurring specific T cells and thus could be a potential target for immunomodulatory cancer ***,we tested healthy donor and cancer patient T cells for spontaneous T-cell responses specifically targeting 3820-mer epitopes derived from TGFβ*** identified numerous CD4^(+)and CD8^(+)T-cell responses against several epitopes in TGFβ.Additionally,several ex vivo responses were *** enriching specific T cells from different donors,we produced highly specific cultures specific to several TGFβ-derived *** CD8^(+)T-cell clones specific for both a 20-mer epitope and a 9-mer HLA-A2 restricted killed epitope peptide were pulsed in HLA-A2+target cells and killed the HLA-A2+cancer cell lines THP-1 and ***,stimulation of THP-1 cancer cells with cytokines that increased TGFβexpression increased the fraction of killed *** conclusion,we have shown that healthy donors and cancer patients harbor CD4^(+)and CD8^(+)T cells specific for TGFβ-derived epitopes and that cytotoxic T cells with specificity toward TGFβ-derived epitopes are able to recognize and kill cancer cell lines in a TGFβ-dependent manner.

关键词： Immune regulation TGFbeta cancer T cells adaptive immunity

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