Fig. 4

Natural compounds targeting immune checkpoints and gut microbiome to serve as cancer chemopreventive agents. a Targeting immune checkpoints. T cells recognize antigens presented by the major histocompatibility complex (MHC) on the surface of cancer cells through their T-cell receptor (TCR). However, this signal is not sufficient to initiate T-cell response and requires a second signal transmitted by the costimulatory molecules of B7. The interaction between cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and costimulatory molecules mainly occurs during the initiation phase of T-cell responses. Programmed death-1 (PD-1) inhibitory receptors are expressed by T cells during long-term antigen exposure and exert negative regulation on T cells during their association with programmed death ligand-1 (PD-L1), and the PD-1 interaction occurs during the effector phase of T-cell responses. The inhibitory effect of natural compounds on tumor can be achieved by interfering with the interaction between PD-L1 or CTLA-4 with their corresponding receptors, and blocking the interaction of related signaling pathways, promoting T-cell activation, thus restoring immune cell function and promoting a strong tumor immune response. b Targeting gut microbiome. The imbalance of gut microbiota is closely related to the development of cancer, tumor growth may lead to local disruption of the barrier, resulting in microbial invasion and immune monitoring disrupted. The gut microbiome regulates various host processes, including metabolism, inflammation, and immunity. Natural compounds can improve cancer-related metabolism, inflammation, and immunity by remodeling gut microbiota homeostasis. DC dendritic cell. This figure was created with Biorender.com, and adapted from Antoni Ribas.⁴⁸²