Co-Colorectal cancer stem cells employ the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia.

Autor: Geng S; Central Laboratory of the People's Hospital of Dazu, The Affiliated Dazu Hospital of Chongqing Medical University, 402360 Chongqing, China., Zhu L; Department of General Surgery, The First People's Hospital of Kunming, 650034 Kunming, Yunnan Province, China., Wang Y; Central Laboratory of the People's Hospital of Dazu, The Affiliated Dazu Hospital of Chongqing Medical University, 402360 Chongqing, China., Liu Q; Department of General Surgery, The Affiliated Dazu Hospital of Chongqing Medical University, 402360 Chongqing, China., Yu C; Department of Hernia Surgery, Qujing No.1 Hospital, 655099 Qujing, Yunnan Province, China., Shi S; Office of Hospital, The Affiliated Dazu Hospital of Chongqing Medical University, 402360 Chongqing, China. Electronic address: shishandazu@163.com., Yu S; Department of General Surgery, The Affiliated Dazu Hospital of Chongqing Medical University, 402360 Chongqing, China. Electronic address: ysh197458@sina.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 25; Vol. 143 (Pt 3), pp. 113535. Date of Electronic Publication: 2024 Nov 02.
DOI: 10.1016/j.intimp.2024.113535
Abstrakt: Colorectal cancer (CRC) ranks as China's second most common cancer and fifth top cancer death cause. The study highlights the role of Natural Killer (NK) cells in targeting cancer stem cells (CSCs) that evade immune responses in CRC. Colorectal cancer stem cells (CCSCs) were stem from HT-29 cells and co-cultured with NK cells under normoxic or hypoxic conditions. The impact of this co-culture was evaluated using CCK8 assays for NK cell viability, ELISA for cytokine level changes, and flow cytometry for assessing NK cell apoptosis and activation. Comprehensive metabolomic and transcriptomic analyses were also performed to identify key genes and metabolites involved in the interaction between CCSCs and NK cells Co-culture of CCSCs with NK cells under hypoxia reduced NK cytotoxicity, increased NK apoptosis, and altered cytokine secretion by decreasing IFN-γ and TNF-α levels while increasing IL-6. Transcriptomic and metabolomic analysis identified 4 genes (FADS1, ALDH3A2, GCSH, MTCL1) and 3 metabolites (glyoxylic acid, spermine, DDA) as significant. Interfering with FADS1 counteracted the suppression of IFN-γ and TNF-α induced by CSC cells. Curiously, this inhibition caused by si-FADS1 could be neutralized by the addition of exogenous DDA. Co-culturing with NK cells notably increased spermine levels. Exogenous spermine resulted in a significant reduction in HT-29 cell death rates at 32 µM, 64 µM, and 128 µM, compared to NK cells without spermine. Our research explored CCSCs employed the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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