Fig. 3

Role of ROS in innate immunity. ROS have a dual role in innate immunity and can function as either a potential therapeutic target against cancer by inhibiting tumor cell proliferation and promoting innate immune cells or as an obstacle to treatment by promoting tumor cell proliferation and inhibiting innate immune cells. a Promotion. ROS contribute to macrophages becoming M1 phenotype and mediating the phagocytic activity of M1 macrophages by releasing factors such as IL-1, IL-12, and TNF-α. Neutrophils play a crucial role in killing tumor cells and preventing tumor spread and metastasis. ROS generation induces excessive calcium influx in tumor cells through TRPM2 channels, inhibiting tumor cell growth and metastasis and driving the cytotoxic effect of neutrophils. ROS production is an early event after NK cells recognize cancer cells and induce the production of cytotoxic essential substances such as perforin and granzyme. ROS generation in DC cells regulates their phagocytic activity and maintains alkalinization. When tumor cells enter DCs, the activation of STING by tumor cell DNA promotes the production of IFN1 and other defense cytokines. b Suppression. ROS promote macrophage transformation to M2 type and secrete inhibitory cytokines such as IL-10 and TGF-β, which have pro-angiogenic and immunosuppressive functions and promote tumorigenesis. ROS also promote the generation of neutrophil extracellular traps (NETs), which can have both tumor-promoting and metastasis-promoting effects. High ROS levels in the TME may also be detrimental to NK cell survival, and L-kynurenine as well as lactate produced by IDO can lead to NK cell apoptosis through ROS pathways in NK cells. Additionally, excess ROS can oxidize lipids and form lipid bodies (LB) of electrophilic oxidized truncated (ox-tr) lipids, inhibiting antigen presentation by DCs to T cells and weakening immune responses