Understanding the immunomodulatory mechanisms for natural products that overcome tumor chemoresistance to platinum-based cancer drugs and other treatments

Rationale Cancer remains one of the most formidable challenges in mordern medicine. Chemoresistance, particularly resistance to platinum-based agents, presents a major challenge in effective treatments. In response to this issue, cancer immunotherapy has emerged as a treatment approach that boosts the body’s immune system and cellular defenses to eliminate cancer cells, complementing the established pillars of cancer treatment: surgery, radiotherapy, and chemotherapy. Recently, natural products have attracted significant interest for their cancer immunotherapeutic properties as well as their potential to help overcome chemoresistance. Yet the underlying mechanisms remain poorly understood. Objective and Findings In this review, we examine the dual roles of immune cells in tumor proliferation and elimination and discuss the application of natural products in alleviating and overcoming tumor drug resistance, specifically focusing on immunomodulatory mechanisms. Current evidence shows that specific natural products can attenuate chemoresistance by modulating the functions of T cells, macrophages, NK cells, and dendritic cells. Notably, baicalin, naringin, ginsenosides, and atractylenolide I can alleviate platinum resistance via immunomodulation, enhanced apoptosis, and inhibition of oncogenic pathways (NF-κB, PI3K/Akt, STAT3). These compounds show synergistic therapeutic potential in colorectal, lung, and ovarian cancers. Conclusion Immunomodulation represents a promising strategy in overcoming tumor drug resistance. The use natural products as immunomodulatory agents to enhance tumor chemosensitivity may constitute a novel therapeutic strategy, providing a foundation for the development of novel adjuvant cancer therapies.