Mazzoni Alessio, Capone Manuela, Ramazzotti Matteo, Vanni Anna, Locatello Luca Giovanni, Gallo Oreste, De Palma Raffaele, Cosmi Lorenzo, Liotta Francesco, Annunziato Francesco, Maggi Laura
Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
J Clin Med. 2021 May 13;10(10):2111. doi: 10.3390/jcm10102111.
Amino acids have a primary role in cancer metabolism. Beyond their primary biosynthetic role, they represent also an alternative fuel while their catabolites can influence the epigenetic control of gene expression and suppress anti-tumor immune responses. The accumulation of amino-acid derivatives in the tumor microenvironment depends not only on the activity of tumor cells, but also on stromal cells. In this study, we show that mesenchymal stromal cells derived from head-neck cancer express the amino acid oxidase IL4I1 that has been detected in different types of tumor cells. The catabolic products of IL4I1, HO, and kynurenines are known to suppress T cell response. We found that neutralization of IL4I1 activity can restore T cell proliferation. Thus, therapeutical strategies targeting enzymes involved in amino-acid catabolism may be helpful to contemporary block tumor cell migration and restore an efficacious anti-tumor immunity.
氨基酸在癌症代谢中起主要作用。除了其主要的生物合成作用外，它们还是一种替代燃料，而其分解代谢产物可影响基因表达的表观遗传控制并抑制抗肿瘤免疫反应。肿瘤微环境中氨基酸衍生物的积累不仅取决于肿瘤细胞的活性，还取决于基质细胞。在本研究中，我们表明源自头颈癌的间充质基质细胞表达已在不同类型肿瘤细胞中检测到的氨基酸氧化酶IL4I1。已知IL4I1、HO和犬尿氨酸的分解代谢产物会抑制T细胞反应。我们发现中和IL4I1活性可恢复T细胞增殖。因此，针对参与氨基酸分解代谢的酶的治疗策略可能有助于同时阻断肿瘤细胞迁移并恢复有效的抗肿瘤免疫力。
