Natural products (NPs) have long been a cornerstone of anticancer drug discovery; yet their systematic integration into cancer immunotherapy remains limited. This review offers a mechanistic and classification-based perspective, organizing representative NPs, specifically polysaccharides, flavonoids, terpenoids, and alkaloids-according to their distinct immunomodulatory mechanisms within the tumor immune microenvironment. We elucidate how NPs reshape the immune landscape throughout the process of cancer immunoediting, enhancing immune cell infiltration, activating effector responses, and reprogramming cytokine signaling networks. In addition to their potential as single agents, we highlight emerging combination strategies in which NPs synergize with immune checkpoint inhibitors or serve as payloads in antibody-drug conjugates to overcome immunosuppression and therapeutic resistance. By integrating insights across structural classes and functional pathways, this review establishes a cohesive framework linking NP pharmacology with immuno-oncology, aiming to guide the rational design of NP-based combination immunotherapies and accelerate their clinical translation.
Liu et al. (Wed,) studied this question.