Tumor Microenvironment of Gynecological Tumors

Dear Colleagues,

The tumor microenvironment (TME) of gynecological cancers, including ovarian, uterine, endometrial, and cervical cancers, plays a crucial role in tumor progression, immune evasion, and therapeutic resistance. This dynamic ecosystem consists of cancer cells, immune cells, cancer-associated fibroblasts (CAFs), endothelial cells, and extracellular matrix components that interact to modulate tumor behavior.

Immunomodulation within the TME enables tumor cells to evade immune surveillance by suppressing cytotoxic T cells and recruiting immunosuppressive regulatory T cells and myeloid-derived suppressor cells. Cancer-associated fibroblasts contribute to tumor progression by secreting growth factors and remodeling the extracellular matrix, promoting invasion and metastasis. Endothelial cells drive angiogenesis, ensuring a continuous supply of oxygen and nutrients to support tumor growth while also forming an abnormal vasculature that impairs drug delivery.

Metastatic niches in gynecological cancers, such as the omental and peritoneal environments in ovarian cancer or the lymphatic spread in cervical cancer, provide a supportive microenvironment for disseminated tumor cells. These niches are preconditioned by tumor-derived exosomes, cytokines, and extracellular matrix remodeling, creating a permissive site for colonization and growth. The interplay between metastatic niches and the TME further enhances tumor plasticity and resistance to therapy.

Critical signaling pathways within the gynecological TME regulate tumor progression and therapeutic responses. The transforming growth factor-beta (TGF-β) pathway promotes immune suppression and CAF activation, while the PI3K/AKT/mTOR pathway drives tumor cell survival and angiogenesis. The Wnt/β-catenin signaling axis is implicated in immune evasion by altering T-cell infiltration, and the hypoxia-inducible factor-1 alpha (HIF-1α) pathway facilitates adaptation to hypoxic conditions, promoting tumor aggressiveness. Understanding these pathways enables the discovery of potential therapeutic targets to disrupt the pro-tumorigenic functions of the gynecological TME.

Prof. Dr. Zahid Pranjol
Dr. Dmitry Aleksandrovich Zinovkin
Guest Editors

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