Gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating FBP1.
Gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating FBP1.
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DOI：
10.5114/ceji.2021.111753
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Zhu W
中科院分区：
文献类型：
--
作者：
Han F;Guo S;Huang C;Cui L;Zhao Y;Ma J;Zhu M;Chen Z;Wang M;Shen B;Zhu W
自然杀伤（NK）细胞的功能障碍已被广泛报道的恶性肿瘤，包括实体瘤。胃癌间充质干细胞（gastric cancer mesenchymal stem cells，GCMSCs）是肿瘤环境（tumor environment，TME）中重要的基质细胞之一，具有免疫抑制活性。本研究旨在探讨GCMSCs是否参与了NK细胞免疫功能的抑制并探讨其机制。流式细胞术检测GCMSCs-CM致敏的NK细胞CD 107 a和穿孔素的表达。为了确定NK细胞的细胞毒性，使用CytoTox 96非放射性细胞毒性测定试剂盒。通过葡萄糖摄取和乳酸产生测定来评估GCMSCs-CM处理的NK细胞的代谢状态。通过免疫印迹分析NK细胞中FBP 1的表达。GCMSCs抑制NK细胞的脱颗粒能力、穿孔素产生和细胞毒性。GCMSCs-CM抑制NK细胞的葡萄糖摄取和乳酸产生，从而削弱其糖酵解代谢。在GCMSCs-CM存在下，NK细胞的FBP 1表达上调。使用FBP 1抑制剂可以逆转NK细胞的功能失调状态。本研究表明GCMSCs可通过上调FBP 1表达对NK细胞发挥免疫抑制作用，为基于NK细胞的GC免疫治疗开辟了新途径。
The dysfunction of natural killer (NK) cells has been widely reported in malignancies, including in solid tumours. Gastric cancer mesenchymal stem cells (GCMSCs) are one of the vital elements of stromal cells in the tumour environment (TME) which possess immunosuppressive activity. This study aimed to determine whether GCMSCs are involved in the inhibition of NK cell immune function and explore its underlying mechanism. CD107a and perforin expression of GCMSCs conditioned medium (GCMSCs-CM)-primed NK cells were detected by flow cytometry. To determine NK cell cytotoxicity, the CytoTox96 Non-Radioactive Cytotoxicity Assay kit was used. Glucose uptake and lactate production assay were performed to evaluate the metabolism state of NK cells treated with GCMSCs-CM. The expression of FBP1 in NK cells was analysed by immunoblotting. GCMSCs inhibited the degranulation capacity, perforin production and cytotoxicity of NK cells. GCMSCs-CM restrained NK cell glucose uptake and lactate production, thus weakening their glycolytic metabolism. FBP1 expression of NK cells was upregulated in the presence of GCMSCs-CM. Using FBP1 inhibitor could reverse the dysfunctional state of NK cells. This study indicated that GCMSCs could exert immunosuppressive effects on NK cells by up-regulating FBP1 expression, opening up new avenues for NK cell-based GC immunotherapy.
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影响因子：
28.2
作者：
Cózar B;Greppi M;Carpentier S;Narni-Mancinelli E;Chiossone L;Vivier E
通讯作者：
Vivier E
影响因子：
8
作者：
Li, Bailiang;Jiang, Yuming;Li, Ruijiang
通讯作者：
Li, Ruijiang
影响因子：
4.3
作者：
Guo S;Huang C;Han F;Chen B;Ding Y;Zhao Y;Chen Z;Wen S;Wang M;Shen B;Zhu W
通讯作者：
Zhu W
影响因子：
39.3
作者：
Shi L;Huang H;Lu X;Yan X;Jiang X;Xu R;Wang S;Zhang C;Yuan X;Xu Z;Huang L;Fu JL;Li Y;Zhang Y;Yao WQ;Liu T;Song J;Sun L;Yang F;Zhang X;Zhang B;Shi M;Meng F;Song Y;Yu Y;Wen J;Li Q;Mao Q;Maeurer M;Zumla A;Yao C;Xie WF;Wang FS
通讯作者：
Wang FS
影响因子：
10.9
作者：
Slattery K;Woods E;Zaiatz-Bittencourt V;Marks S;Chew S;Conroy M;Goggin C;MacEochagain C;Kennedy J;Lucas S;Finlay DK;Gardiner CM
通讯作者：
Gardiner CM