Concerted regulation of STAT3 and STAT5 activation in CD8 T effector and memory cells has been shown to impact their tumor-specific responses including intra-tumor accumulation, long-term survival, cytotoxic activity and resistance toward tumor-derived immune suppression.
However, recent studies have shown that STAT3 activation leads to upregulation of program death receptor-ligand 1 (PD-L1, an immune checkpoint protein that plays a major role behind evasion of immune systems by growing tumors) expression levels in tumor cells, leading to enhanced immune suppression.
Here we provide an update on novel insights into the role of STAT3 in immune suppression and describe current therapeutic strategies that target the JAK/STAT3 signaling axis for the treatment of malignancies.
STAT3 has many roles in physiological processes such as inflammatory signalling, aerobic glycolysis and immune suppression, and was also the first family member shown to be aberrantly activated in a wide range of both solid and liquid tumours.
Targeting blockage of STAT3 in hepatocellular carcinoma cells augments NK cell functions via reverse hepatocellular carcinoma-induced immune suppression.