二甲雙胍增強(qiáng)體外擴(kuò)增γST細(xì)胞的抗腫瘤活性

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Abstract：Gamma delta （yδ） Tcellsare a subset ofTlymphocytes expressing γδT cell receptors，which possess both innate andadaptiveimmune functions.Theycanrecognizeandkilltumor cells inamanner independentlyofMHCrestriction. However，theirlimitedquantityinvivoandlowefficiencyinvitroexpansionrestricttheirclinicalapplication.Thisstudy utilizedacombinationofcytokinesinterleukin-2（I-2）nterleukin-15（-15），ndtebisphosphonatedugzoledrocacid （Zol） to stimulate γδT cellsand optimize their in vitro expansion strategy.Results demonstrated that thecombination of Zol （5μmol/L） ，IL-2（ 100IU/mL ，andIL-15 Δ10ng/mL ）achieveda10 ooo-foldexpansion of γδT cells，with a purity of 95.74% among CD3-positivecels.Additionally，metformintreatmentsignificantlyincreasedtheproportionsofcentralmemorycell subsets from 10.75% to 15.85% and effector memory cell subsets from 5.98% to 19.30% in γδT cells ）.Metformin also markedly upregulated the expression of anti-tumor factors interferon ?γ （IFN-γ） ， granzyme B （GZMB），and perforin in γδT cels，promotedexosomesecretion，andeancedcytotoxicactivity.Thisstudyprovidesanovelstrategyforinvitropansion and functional optimization of γδT cells，laying the foundation for their application in adoptive immunotherapy for tumors.

Key words： γδT cells; antitumor activity; metformin; anti-tumor factor; adoptive immunotherapy （ActaLaser Biology Sinica，2025，34（3）：229-238）

γδT 細(xì)胞是具有 γ 鏈和8鏈組成的T細(xì)胞受體（Tcellreceptor，TCR）表達(dá)的T細(xì)胞亞群，在外周血的CD3 陽性細(xì)胞里所占比例為 5%～10%[1-3] 。（剩余21183字）