Table 1.

The main sequence of events occurring in the TME

No.	Parameter	Initial result	Subsequent result	Reference
1	Angiogenesis	Leaky vessels	Hypoxia	[6]
2	Hypoxia	Induce HIF	Increased angiogenesis	[8]
3	Insufficient glucose	Anaerobic glycolysis	Lactate increase	[9]
4	Excessive lactate	Increased acidity	Increased influx of MDSCs, TAMs, Tregs*	[10]
5	Anaerobic glycolysis	Lactate increase	Acidity increase	[7]
6	Poor pericytes	Leaky vessels	Increased 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