The main sequence of events occurring in the TME

No.ParameterInitial resultSubsequent resultReference
1AngiogenesisLeaky vesselsHypoxia[6]
2HypoxiaInduce HIFIncreased angiogenesis[8]
3Insufficient glucoseAnaerobic glycolysisLactate increase[9]
4Excessive lactateIncreased acidityIncreased influx of MDSCs, TAMs, Tregs*[10]
5Anaerobic glycolysisLactate increaseAcidity increase[7]
6Poor pericytesLeaky vesselsIncreased interstitial fluid pressure[7]

Items 1 and 2 would readily form a vicious cycle of angiogenesis, hypoxia, worse angiogenesis, worse hypoxia, etc. * together, these cells would significantly reduce host immunity; HIF: hypoxia-inducible factor; MDSCs: myeloid-derived suppressor cells; TAMs: tumor-associated macrophages; Tregs: regulatory T cells