Strategies of cancer cell glucose metabolism in determining cd8+ t cell reprogramming in the ovarian cancer tumor microenvironment

Kusumastuti, Sanindita and Siregar, Nurjati Chairani and Hellyanti, Tantri and Kodariah, Ria (2025) Strategies of cancer cell glucose metabolism in determining cd8+ t cell reprogramming in the ovarian cancer tumor microenvironment. World Journal of Advanced Research and Reviews, 25 (2). pp. 1063-1071. ISSN 2581-9615

Ovarian cancer is the leading cause of death among gynecological neoplasm due to its high proliferation rate and invasive ability. This elevated proliferation rate correlates with increased glycolytic activity, a mechanism also utilized by CD8+ T cells, which serves as the body’s primary line of defense against cancer. Elevated glycolysis in ovarian cancer cells is primarily due to PIK3CA mutation, one of the most frequently mutated genes in ovarian cancer. Other mutations contributing to elevated glycolysis include FOXM1, SIK2, and PTGES3, all of which lead to increased glucose uptake and upregulation of glycolytic enzyme expression. CD8+ T cell activation results in metabolic reprogramming that enhances glycolytic activity, which is important for maintaining their effector functions. In the scarcity of glucose, GAPDH enzyme binds to IFN-g mRNA, inhibiting its translation. Lactate accumulation in tumor microenvironment decreases granzyme secretion and inhibits proliferation and infiltration of effector CD8+ T cells. Similar metabolic profiles between ovarian cancer cells and effector CD8+ T cells result in nutrient deficiency and accumulation of lactate in tumor microenvironment, which leads to effector CD8+ T cells’ dysfunction, thereby contributing to immune escape. Intervention in T cell metabolic reprogramming may present opportunity to improve their cytotoxicity toward cancer cells.