Editorial: Immunomodulatory molecules of natural origin: innovative strategies for combatting cancer

Abstract

Cancer remains a major global health challenge, reinforcing the need for innovative therapeutic strategies to achieve better outcomes. Despite existing traditional therapies such as radiation therapy, chemotherapy, and photodynamic therapy, cancer mortality rates continue to rise each year. Recently, immunotherapy has gained significant attention for its role in reactivating antitumour immune responses to combat and control cancer. Based on target specificity, immunotherapy strategies are divided into two categories: specific and nonspecific. Specific immunomodulators, such as vaccines, are designed to target a specific antigen. In contrast, nonspecific immunomodulators enhance the anticancer immune response by activating both the innate and adaptive immune systems and by modulating immune cells such as macrophages, dendritic cells, and T lymphocytes, and also the tumour microenvironment (TME). Immune checkpoint inhibitors, such as antibodies targeting Programmed Death-1 (PD-1)/Programmed Death-Ligand 1 (PD-L1), and Chimeric Antigen Receptor T (CAR-T) cell therapy, have markedly enhanced treatment outcomes (1). However, despite these advancements, many patients remain unresponsive or only partially respond to treatments, and some develop immune-related adverse events (irAEs). This underscores the urgent need to develop new immunomodulators with enhanced safety profiles. Phytomolecules currently being tested in clinical trials, such as Apigenin, Berberine, Epigallocatechin gallate (EGCG), Curcumin, Resveratrol, and Ginsenoside Rh2, have shown the potential in preclinical studies to trigger an immune response against cancer via the PD-1/PD-L1 pathway (2). Apigenin can promote the proliferation of T lymphocytes and induce T-cell-mediated cell death in breast cancer and melanoma cells. It can also increase CD4+ and CD8+ T-cell infiltration in melanoma (B16-F10)-bearing mice, stimulating T-cell immunity by decreasing PD-L1 expression (3, 4). Myeloid-derived suppressor cells (MDSCs) and Treg cells are potent immunosuppressive cells that facilitate immune evasion in the immunosuppressive tumour microenvironment (TME) by suppressing T-cell activity.