Author(s)

Rui Liang

Corresponding Author

Rui Liang

ABSTRACT

TGF-beta, as a transcriptional factor can regulate the populations of different type of immune cells. Via activation several biochemical cascade (P38/JNK, AKT, ERK), more Treg cells, which act as immune suppressors, are expressed at a higher level; and the cytotoxic immune cells apoptosis also happens. Consistent with the effects of Treg cells, both CD4+ and CD8+ cells which express dominant­negative form of TGF-beta receptor have been reported to have stronger cancer immunity. Hypoxia, on the other hand, is another typical condition of solid tumours. As the cytotoxic immune cells usually depends on both glucose and oxygen to function, the immunity of such cells is usually weakened under hypoxia. Also, hypoxia can let the immune cells down regulate cytotoxic enzyme. Lactates over production can be a consequence of hypoxia, nevertheless, it impacts the immune cells’ function through way. Besides expression of Treg cells, it can also down regulate the glycolysis of CD8+ cells. The capability of CD8+ cells to proliferate and produce cytokine are weakened. Furthermore, the macrophages are affected and shift to M2 state in presence of highly concentrated lactate, and M2 activated macrophage can confer the tumour cells extra immune resisitence. This paper aims to revisit and summary the studies which review the mechanism underlying the limitations of the adaptive system in solid tumour. There are three major aspects that been covered by this paper: TGF-beta, hypoxia, and lactate.

KEYWORDS

Solid tumour, adaptive immune, immunotherapy, cancer