Immunomodulatory Role of Propolis in Hypoxia and in the Tumor Microenvironment

Propolis is a well-known sticky, resinous substance collected by honeybees (Apis mellifera) from the buds of trees and other plants, then mixed with beeswax and their own glandular secretions. Its chemical composition varies widely depending on the bee species, geographic location, plant sources, and weather conditions. The therapeutic potential of propolis-including antimicrobial, anti-inflammatory, and anticancer effects-has been recognized since antiquity. Cancer remains one of the leading causes of morbidity and mortality worldwide. High levels of hypoxia within tumor tissue significantly contribute to cancer progression and increase the resistance of tumor cells to radio- and chemotherapy. In the tumor microenvironment, cytokines play key roles in processes such as invasion, metastasis, and immune suppression. The concept of the "cytokine field" describes how elevated cytokine levels within the tumor microenvironment create a field effect, influencing surrounding cells. Current research is exploring the use of natural immunomodulators, such as propolis, in combination with conventional chemotherapeutic agents for cancer treatment. This review summarizes the potential immunomodulatory role of propolis within the tumor microenvironment.