STAT3 inhibitors offer a promising approach in modern cancer therapy. However, the rapid degradation of these small molecules reduces their effectiveness. Immune checkpoint inhibitors that are also used in combination with STAT3 inhibitors target the T-lymphocytes as main drivers for anti tumor immunity. The influence of natural killer cells should not be disregarded.
STAT3 mediates between tumor cell and immune cell
STAT3 inhibitors are used in solid tumors as well as in blood cancers. STAT3 refers to the signal transduction and activation of transcription 3 as part of a complex metabolic pathway in cancer. A team of authors led by the Karl Landsteiner University with the Division of Pharmacology has summarised the effects of STAT3 on the dynamic interaction between natural killer cells and tumor cells. This literature review has been published in the renowned journal "Frontiers in Immunology".
STAT3 helps tumor cell to “hide”
Natural killer cells as part of the innate immune system can eliminate other cells (tumor cells, virus-infected cells. ...) . To escape the surveillance of the natural killer cells, tumor cells reduce the release of substances that would activate the natural killer cells. For this they use the cell internal STAT3 mechanism. Numerous cell studies have shown that by inhibiting STAT3, the tumor cell is better recognised by natural killer cells and thus combated.
STAT3 affects tumor cells, natural killer cells and components of the microenvironment
STAT3 inhibition inside the NK cell leads to more natural killer cell receptors and thus to efficient recognition of the tumor cell. In the microenvironment of the tumor the inhibition of STAT3 usually has also an immune-promoting effect. There is an increased release of pro-inflammatory substances, which in turn activate the natural killer cells. The extent of STAT3 activation or inhibition thus influences the anti-tumor effect of the natural killer cells. However, the expected increased immune response through STAT3 inhibition depends on tumor type and biological context.
Increased anti-tumor immunity through better understanding
Various STAT3 inhibitors to fight tumors are currently being tested in clinical trials. STAT3 protects the tumor cell from recognition by natural killer cells and influences the tumor's microenvironment in its favour. To boost anti-tumor immunity in natural killer cells, knowledge of the multiple effects of STAT3 inhibition and its impact on natural killer cells in humans is highly important.