小柯机器人

美国斯隆·凯特琳纪念癌症中心Ed Reznik研究小组发现，免疫代谢协同演变定义透明细胞肾细胞癌（ccRCC）的独特微环境。该研究于2023年7月5日在线发表于国际一流学术期刊《细胞—代谢》。

为了研究瘤内代谢物异质性（IMH），研究人员对ccRCC患者的肿瘤/正常区域进行了分析。一个共同的IMH模式超越了所有患者，其特点是代谢物丰度的相关波动和与铁死亡有关的过程。对瘤内代谢物-RNA共变的分析表明，微环境的免疫组成，特别是骨髓细胞的丰度，推动了瘤内代谢物的变化。

由于RNA-代谢物共变的强度和RNA生物标志物在ccRCC中的临床意义，研究人员从参加7项临床试验的ccRCC患者RNA测序数据中推断出代谢组谱，并最终确定了与抗血管生成药物反应相关的代谢物生物标志物。因此，局部代谢表型与免疫微环境同步出现，影响正在进行的肿瘤演变，并与治疗敏感性相关。

据悉，肿瘤细胞的表型和抗肿瘤免疫反应是由局部代谢物的可用性决定的，但对IMH及其表型后果仍知之甚少。

附：英文原文

Title: Immunometabolic coevolution defines unique microenvironmental niches in ccRCC

Author: Cerise Tang, Amy X. Xie, Eric Minwei Liu, Fengshen Kuo, Minsoo Kim, Renzo G. DiNatale, Mahdi Golkaram, Ying-Bei Chen, Sounak Gupta, Robert J. Motzer, Paul Russo, Jonathan Coleman, Maria I. Carlo, Martin H. Voss, Ritesh R. Kotecha, Chung-Han Lee, Wesley Tansey, Nikolaus Schultz, A. Ari Hakimi, Ed Reznik

Issue&Volume: 2023-07-05

Abstract: Tumor cell phenotypes and anti-tumor immune responses are shaped by local metabolite availability, but intratumoral metabolite heterogeneity (IMH) and its phenotypic consequences remain poorly understood. To study IMH, we profiled tumor/normal regions from clear cell renal cell carcinoma (ccRCC) patients. A common pattern of IMH transcended all patients, characterized by correlated fluctuations in the abundance of metabolites and processes associated with ferroptosis. Analysis of intratumoral metabolite-RNA covariation revealed that the immune composition of the microenvironment, especially the abundance of myeloid cells, drove intratumoral metabolite variation. Motivated by the strength of RNA-metabolite covariation and the clinical significance of RNA biomarkers in ccRCC, we inferred metabolomic profiles from the RNA sequencing data of ccRCC patients enrolled in 7 clinical trials, and we ultimately identifyied metabolite biomarkers associated with response to anti-angiogenic agents. Local metabolic phenotypes, therefore, emerge in tandem with the immune microenvironment, influence ongoing tumor evolution, and are associated with therapeutic sensitivity.

DOI: 10.1016/j.cmet.2023.06.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00215-2

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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