Blocking STAT3 may increase antitumor immune response

Blocking STAT3 in cells of the immune system actually leads to increased antitumor immunity, according to new research. STAT3 is frequently activated in tumor cells, and these new findings further suggest that anti-STAT3 therapy may be highly promising.

The so-called signal transducers and activators of transcription, or STATs, are key components of many different signaling pathways. Not surprisingly, when something goes wrong with their regulation the consequences can be severe. Many types of cancer are known to be associated with increased activities of one or more STAT protein. STAT3 is a frequent culprit and is often found activated in tumor cells. Considerable efforts are going into developing inhibitors of STAT3 for use in cancer therapy but it is unclear whether these will turn out to be suitable for use in patients.

The problem is that STAT3 also has a number of crucial functions in the healthy body. In particular, it is important for the development of several kinds of cells of the immune system. This includes the natural killer (NK) cells, which represent the first line of defense against viruses and cancer. NK cells react by producing a range of proteins that attack the infected cells. This study investigated how NK cells of the body's own anticancer defense mechanisms respond to inactivating STAT3.

Dagmar Gotthardt and colleagues in the Institute of Pharmacology and Toxicology of the University of Veterinary Medicine, Vienna (Vetmeduni Vienna) found that the loss of STAT3 in NK cells of mice led to an increase in killing activity against melanoma cells and leukemia cells. The decrease in metastasis caused by melanoma cells was especially dramatic and confirmed that NK cells lacking STAT3 are extremely efficient killers of tumor cells.

“We were expecting the loss of STAT3 to make the NK cells less efficient. Instead it makes them even more potent killers. Inhibiting STAT3 could thus help cancer patients in two ways, both stopping the cancer cells from dividing and helping the patients' NK cells to fight them more efficiently,” said Gotthardt. The study was published in Blood (2014; doi:10.1182/blood-2014-03-564450).

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