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Sci Immunol:新方法或能重新激活T細胞來有效抵御癌癥

近日,來自美國弗吉尼亞大學等機構的科學家們通過研究發現了一種新方法,或能重新激活因抵御癌癥而耗盡的T細胞的功能,相關研究刊登于國際雜志Science Immunology上。文章中,研究人員闡明了烯醇化酶1(enolase 1)水平的下降對T細胞所產生的影響,以及如何繞

近日,來自美國弗吉尼亞大學等機構的科學家們通過研究發現了一種新方法,或能重新激活因抵御癌癥而耗盡的T細胞的功能,相關研究刊登于國際雜志Science Immunology上。文章中,研究人員闡明了烯醇化酶1(enolase 1)水平的下降對T細胞所產生的影響,以及如何繞過該影響給機體免疫系統“充電”。

圖片來源:NIAID/NIH

此前研究結果表明,免疫系統有時無法有效抵御癌變的腫瘤組織,因為當腫瘤浸潤性的淋巴細胞(TILs)攻擊腫瘤組織時常常會失去能量,疲憊的T細胞或許就無法有效殺滅癌細胞,從而就會使得腫瘤組織不斷增殖,研究者認為,T細胞或許會因饑餓的腫瘤細胞奪走葡萄糖而變得“無精打采”,這項研究中,他們就找到了一種新方法來克服這種問題,從而讓TILs能夠有效攻擊癌癥。

文章中,研究者對處于休眠狀態和激活狀態的CD8+ TILs進行研究,他們發現,CD8+ TILs在對抗癌細胞一段時間后就會被耗竭,更有意思的是,T細胞的耗竭或許是因為烯醇化酶1水平的下降,該酶存在于葡萄糖代謝通路中,腫瘤細胞會對其進行消耗,從而導致T細胞功能被耗竭,最終就會導致細胞的葡萄糖代謝水平下降以及氧化磷酸化水平下降10倍。

為了重新活化T細胞,研究人員選擇繞過烯醇化酶1,并給予T細胞丙酮酸鹽,丙酮酸鹽是酶類活性的最終產物,隨后研究者發現,細胞的葡萄糖代謝和氧化磷酸化水平增加了,而這也明顯改善T細胞中的能量水平。研究者在活體動物中檢測了一系列檢查點抑制劑的作用效果,他們發現,結合諸如抑制劑類的混合制劑后就能明顯增加活性T細胞的水平,并能有效減緩腫瘤的生長。

下一步研究人員將會進行更為深入的研究來尋找適合在人類機體中使用的合適抑制劑,如果后期研究結果順利的話,未來研究人員或將進一步進行人類臨床試驗。(生物谷Bioon.com)

原始出處:

Lelisa F. Gemta, Peter J. Siska, Marin E. Nelson, et al. Impaired enolase 1 glycolytic activity restrains effector functions of tumor-infiltrating CD8+ T cells, Science Immunology (2019). DOI: 10.1126/sciimmunol.aap9520

 
 
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