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.
Highlights
Ovarian cancer is the common cause of death related to gynecological cancer [1, 2]
Identification of Immunometabolism Subtypes With Prognosis Value in Ovarian Cancer. Lymphocytes, such as CD8+, CD4+ T cells, and natural killer (NK) cells, infiltrating the tumor is a prerequisite for a successful anti-tumor immune response [31]
Immune responses are influenced by tumor metabolism, such as nutrient consumption, increased oxygen consumption, and the production of reactive nitrogen and oxygen intermediates [32]
Summary
Ovarian cancer is the common cause of death related to gynecological cancer [1, 2]. The standard treatment of ovarian cancer is surgical resection with cisplatin-based chemotherapy [3]. About 70% of patients will experience a recurrence within 3 years after first-line treatment [4]. Chemotherapy has maintained its pivotal role in drug therapy for ovarian cancer. Very few new drug strategies have been approved. Poly ADP ribose polymerase (PARP) inhibitors have been approved for maintenance therapy [5].
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