Tumor Immunometabolism Characterization in Ovarian Cancer With Prognostic and Therapeutic Implications

Abstract

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.

The Role of Cancer-Associated Fibroblasts in Ovarian Cancer

“…Furthermore, the WNT/β-catenin signaling pathway is also correlated with resistance to anti-PD-L1 and anti-CTLA4 combined therapy [ 80 ]. Studies have also explored the interaction of metabolism and tumor-immune subtypes [ 81 ]. It has been suggested that upregulation of hormone biosynthesis and low immune cell infiltration are the two main characteristics of the ‘immune-desert–endocrine subtype’, which is negatively correlated with MHC molecules and multiple immune cells, such as dendritic cells, and finally leads to the immune-desert type [ 81 ].…”

“…CXCR2 ligands, including CXCL1 and CXCL2, attract MDSC infiltration in Snail-expressing mice to promote ovarian cancer progression [ 82 ]. Metabolic stress may stimulate impaired antitumor immunity in immune-infiltrating tumors [ 81 ]. iCAF subsets also produce certain cytokines, especially IL-6, which presents a pro-tumor function and is closely associated with chemoresistance and poor prognosis [ 83 ].…”

Prognostic Implication of a Novel Metabolism-Related Gene Signature in Hepatocellular Carcinoma

“…An increasing number of studies have indicated that metabolic reprogramming of tumors is related to immune infiltration and immune responses (16). Therefore, we further investigated whether there were different subgroups of immune cells in the two risk groups and scored the related functions by using ssGSEA.…”

Glycosylation-Related Genes Predict the Prognosis and Immune Fraction of Ovarian Cancer Patients Based on Weighted Gene Coexpression Network Analysis (WGCNA) and Machine Learning

“…Approximately 70% of OC individuals will develop a recurrence after surgery, and about 75% of high-grade serous ovarian cancer (HGSOC) patients will experience chemoresistance against cisplatin, oxaliplatin, carboplatin, etc. [9,10]. Identifying novel risk factors that regulate tumorigenesis, migration, and proliferation will contribute to early diagnosis and personalized interventions for OC treatment.…”