Stoll Gautier, Kremer Margerie, Bloy Normal, Joseph Adrien, Castedo Maria, Meurice Guillaume, Klein Christophe, Galluzzi Lorenzo, Michels Judith, Kroemer Guido
Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France.
Centre de Recherche des Cordeliers, Equipe 11 labellisée Ligue Nationale contre le Cancer, Paris, France.
Oncoimmunology. 2019 Mar 30;8(6):e1571389. doi: 10.1080/2162402X.2019.1571389. eCollection 2019.
The expression of two metabolic enzymes, ., aldehyde dehydrogenase 7 family, member A1 (ALDH7A1) and lipase C, hepatic type (LIPC) by malignant cells, has been measured by immunohistochemical methods in non-small cell lung carcinoma (NSCLC) biopsies, and has been attributed negative and positive prognostic value, respectively. Here, we demonstrate that the protein levels of ALDH7A1 and LIPC correlate with the levels of the corresponding mRNAs. Bioinformatic analyses of gene expression data from 4921 cancer patients revealed that the expression of LIPC positively correlates with abundant tumor infiltration by myeloid and lymphoid cells in NSCLC, breast carcinoma, colorectal cancer and melanoma samples. In contrast, high levels of ALDH7A1 were associated with a paucity of immune effectors within the tumor bed. These data reinforce the notion that the metabolism of cancer cells has a major impact on immune and inflammatory processes in the tumor microenvironment, pointing to hitherto unsuspected intersections between oncometabolism and immunometabolism.
通过免疫组化方法在非小细胞肺癌（NSCLC）活检组织中检测了两种代谢酶的表达，即醛脱氢酶7家族成员A1（ALDH7A1）和肝型脂肪酶C（LIPC），并分别赋予了它们阴性和阳性的预后价值。在此，我们证明ALDH7A1和LIPC的蛋白质水平与相应mRNA的水平相关。对4921例癌症患者的基因表达数据进行生物信息学分析发现，LIPC的表达与NSCLC、乳腺癌、结直肠癌和黑色素瘤样本中髓样和淋巴细胞的大量肿瘤浸润呈正相关。相反，高水平的ALDH7A1与肿瘤床内免疫效应细胞的缺乏有关。这些数据强化了这样一种观念，即癌细胞的代谢对肿瘤微环境中的免疫和炎症过程有重大影响，指出了肿瘤代谢和免疫代谢之间迄今未被怀疑的交叉点。
