Yang Miner, Chen Gaowen, Gao Kunjie, Wang Yifeng
Department of Gynecology, Obstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Front Oncol. 2021 Mar 16;11:622752. doi: 10.3389/fonc.2021.622752. eCollection 2021.
Metabolic dysregulation in the tumor microenvironment has significant impact on immune infiltration and immune responses. However, interaction between immunity and metabolism in the ovarian microenvironment requires further exploration. We constructed an immunometabolism gene set and ovarian cancer cohort from The Cancer Genome Atlas (TCGA) and classified these into three immunometabolism subtypes. We explored the relationships between immune infiltration and metabolic reprogramming. Additionally, we built risk score and nomogram as prognostic signatures. Three distinctive immunometabolism subtypes were identified with therapeutic and prognostic implications. Subtype 1, the "immune suppressive-glycan metabolism subtype," featured high levels of immunosuppressive cell infiltration and glycan metabolism activation; Subtype 2, the "immune inflamed-amino acid metabolism subtype," showed abundant adaptive immune cell infiltration and amino acid metabolism activation; Subtype 3, the "immune desert-endocrine subtype," was characterized by low immune cell infiltration and upregulation of hormone biosynthesis. Furthermore, we found that epinephrine biosynthesis displayed a significantly negative correlation with MHC molecules, which may result in defective antigen presentation. We proposed immunometabolism subtypes with prognostic implications and provided new perspectives for the ovarian cancer microenvironment.
肿瘤微环境中的代谢失调对免疫浸润和免疫反应有重大影响。然而,卵巢微环境中免疫与代谢之间的相互作用仍需进一步探索。我们从癌症基因组图谱(TCGA)构建了一个免疫代谢基因集和卵巢癌队列,并将其分为三种免疫代谢亚型。我们探讨了免疫浸润与代谢重编程之间的关系。此外,我们构建了风险评分和列线图作为预后特征。识别出了三种具有治疗和预后意义的独特免疫代谢亚型。亚型1为“免疫抑制-聚糖代谢亚型”,其特征是高水平的免疫抑制细胞浸润和聚糖代谢激活;亚型2为“免疫炎症-氨基酸代谢亚型”,表现为丰富的适应性免疫细胞浸润和氨基酸代谢激活;亚型3为“免疫荒漠-内分泌亚型”,其特征是免疫细胞浸润低和激素生物合成上调。此外,我们发现肾上腺素生物合成与MHC分子呈显著负相关,这可能导致抗原呈递缺陷。我们提出了具有预后意义的免疫代谢亚型,为卵巢癌微环境提供了新的视角。