Fig. 4

Disruptor of the virtuous cycle: the cancer-immunometabolism subcycle. In fact, antigen release occurs consistently in most patients with malignant tumors. Nevertheless, the CI cycle of Chen et al. suggests that it does not imply that the inevitable occurrence of cancer cell death events (the left cycle). Metabolic-related factors may be responsible for the disruption of the CI cycle. Considering the cancer-immunometabolism subcycle (the right cycle) proposed in this review, it is reasonable to assume that metabolism-related factors may contribute to the interruption of the CI cycle (the left cycle). When immune cells reach the tumor microenvironment through the vascular endothelium or basement membrane, nutrient deprivation as well as accumulation of local toxic substances accelerate the formation of tumor immunosuppressive microenvironment. Thereby, the infiltrating immune cells become dysfunctional, such as altered macrophage polarization, diminished killing effect of T cells and NK cells, and formation of NETs, and so on. As the result, the CI cycle is impaired and failed to stimulate a potent and sustainable immune response. CI cycle, cancer-immunity cycle; NK cells, natural killer cells; NETs, neutrophil extracellular traps