Metabolism-driven Immune Escape Defines Therapeutic Vulnerability in Type I and Type II Ovarian Cancer.
Ovarian cancer is a heterogeneous disease characterized by diverse molecular, metabolic, and immunological features, which contribute to limited and inconsistent responses to immunotherapy. Recent advances in cancer metabolism have revealed that metabolic reprogramming plays a pivotal role in shaping the tumor immune microenvironment. This review aims to summarize recent progress in understanding how distinct metabolic programs in Type I and Type II ovarian cancer regulate immune escape and determine therapeutic vulnerability, with a particular focus on immunotherapy-related implications. This review is based on selective searches of the scientific literature published mainly within the past decade, using databases such as PubMed and Scopus. Relevant original and review articles addressing ovarian cancer metabolism, tumor immunology, immune checkpoint inhibition, and translational therapeutic strategies were analyzed and integrated. Type I ovarian cancer is characterized by glycolysis-dominant metabolism, frequently associated with ARID1A loss and PI3K/AKT/mTOR pathway activation, leading to nutrient competition and lactate-mediated immune suppression. However, immune infiltration is often preserved, indicating potentially reversible immune dysfunction. In contrast, Type II ovarian cancer exhibits strong dependence on lipid metabolism and adapts to adipocyte-rich metastatic niches, resulting in profound immune exclusion. Growth factor-mediated survival signaling further reinforces resistance to immune-mediated cytotoxicity. These metabolic differences critically influence responses to immune checkpoint inhibitors and provide a biological rationale for subtype-specific combination strategies. Metabolic reprogramming represents a central determinant of immune escape and immunotherapy responsiveness in ovarian cancer. Recognizing the distinct metabolic-immune landscapes of Type I and Type II tumors supports the development of precision immunotherapy strategies that integrate metabolic targeting with immune modulation. Such an approach may help overcome therapeutic resistance and improve clinical outcomes in ovarian cancer.