Abstract:

The tumor microenvironment (TME) is a pivotal regulator in the initiation, progression, recurrence, and chemoresistance of ovarian cancer. Its cellular constituents, cytokine networks, metabolic status, and immune functions undergo profound dynamic alterations during cytoreductive surgery and chemotherapy, this dynamics have not been adequately considered in clinical practice. The pretreatment baseline TME is characterized by immune suppression, stromal activation, and metabolic reprogramming. It features an enrichment of M2-type macrophages and regulatory T cells, impaired function of CD8+ T cells, persistent activation of cancer-associated fibroblast (CAF) that remodel the extracellular matrix, as well as metabolic disorders such as hypoxia and lactate accumulation. Immunosuppressive factors are enriched in the ascites microenvironment. While surgery can reduce the tumor burden and transiently activate CD8+ T cells in the short term, surgical trauma and stress induces a long-term inflammatory and immunosuppressive state. Short-term chemotherapy may promote an immunologically "hot" state by inducing immunogenic cell death and stimulating antitumor immunity. However, prolonged chemotherapy leads to CAF activation and upregulation of programmed death-ligand 1, ultimately driving the TME back into an immunosuppressive state. The dynamic evolution of the TME is closely associated with prognosis. A pro-inflammatory state in the early postoperative period followed by a resurgence of immunosuppression in the mid-term, and the immune state shifting from "hot" to "cold" after chemotherapy, all contribute to the aggravation of recurrence and therapeutic resistance. Therefore, developing TME-targeted therapeutic strategies may open new avenues for optimizing precision treatment in ovarian cancer.

Key words: Ovarian neoplasms, Carcinoma, Tumor microenvironment, Cytoreduction surgical procedures, Drug therapy, combination, Immune tolerance, Drug resistance, neoplasm