Interleukin-6 Is a Crucial Factor in Shaping the Inflammatory Tumor Microenvironment in Ovarian Cancer and Determining Its Hot or Cold Nature with Diagnostic and Prognostic Utilities.

Abstract

Ovarian cancer (OC) remains the leading cause of cancer-related deaths among women, often diagnosed at advanced stages due to the lack of effective early diagnostic procedures. To reduce the high mortality rates in OC, reliable biomarkers are urgently needed, especially to detect OC at its earliest stage, predict specific drug responses, and monitor patients. The cytokine interleukin-6 (IL6) is associated with low survival rates, treatment resistance, and recurrence. In this review, we summarize the role of IL6 in inflammation and how IL6 contributes to ovarian tumorigenesis within the tumor microenvironment, influencing whether the tumor is subsequently classified as "hot" or "cold". We further dissect the molecular and cellular mechanisms through which IL6 production and downstream signaling are regulated, to enhance our understanding of its involvement in OC development, as well as OC resistance to treatment. We highlight the potential of IL6 to be used as a reliable diagnostic biomarker to help detect OC at its earliest stage, and as a part of predictive and prognostic signatures to improve OC management. We further discuss ways to leverage artificial intelligence and machine learning to integrate IL6 into diverse biomarker-based strategies.