Fig. 1

Diagrammatic presentation of the role of SP, NK1R and PKM2 in chronic inflammation in cancer. a). SP/NK1R complex mechanisms in chronic inflammation. SP/NK1R complex regulates immune cell function via neurogenic and nonneurogenic pathways; neurogenic inflammation occurs through the modification of inflammatory cells such as mast cells, lymphocytes, monocytes, and macrophages in tumor and peritumoral tissues. Promotion of nonneurogenic inflammation occurs through activation of macrophages and eosinophils. Additionally, SP acts as a direct proinflammatory cytokine, thus enhancing inflammation in tumor tissues. Lastly, SP/NK1R complex causes genetic modulation through transactivation of receptors with tyrosine kinase activity such as EGFR and HER2, and regulation of proinflammatory transcription factors such as NFkB, cytokines, and chemokines. b). PKM2 mechanisms in chronic inflammation. PKM2 activates proinflammatory transcription factors such as Akt, HIF-1a, p300, β-catenin, and NFkB. Moreover, it promotes aerobic glycolysis which results in activation of E1F2AK2-dependent NRR family and the release of proinflammatory cytokines such as IL-18, IL-1B, and HMBG1, and the activation of inflammasomes in TMAs. Lastly, PKM2-mediated Warburg effect and immunometabolic reprogramming causes activation of immune cells and promotes the secretion of cytokines and proinflammatory mediators