The Role of STAT1 in Immune Escape of Colorectal Cancer

Malignancies are among the leading cause of morbidity and mortality worldwide. Despite the development of targeted therapies that block specific cancer-causing molecules, mortality is expected to rise over the next two decades. Great hopes are pinned on immunotherapy which is an attempt to kill cancer cells via activation of the patients immune system. Tumors consist not only of cancer cells but also surrounding cells which are part of the so-called tumor stroma. Immune cells, which have the potential to attack cancer cells, are also present in the stroma. However, tumors have developed strategies to escape from immune attack and to profit from the presence of immune cells because they produce factors that support tumor growth. Such tumors might not respond to immunotherapy. The research group of Robert Eferl, an Associate Professor and Principal Investigator at the Institute of Cancer Research, Medical University Vienna, has discovered an unexpected function of the transcription factor STAT1 in colorectal tumors. STAT1 seems to promote formation of specific cancer cells that prevent anti-tumor immune attack. The stand-alone FWF grant application The Role of STAT1 in Immune Escape of Colorectal Cancer by Robert Eferl indents to characterize these cancer cells. Targeting these cells or STAT1 should make tumors vulnerable to immune attack and greatly enhance the efficacy of cancer immunotherapy.

Cancer is a leading cause of death worldwide. Despite the development of targeted cancer therapies that block certain cancer-causing molecules, it is believed that the death rate will continue to rise over the next two decades. Great hopes are placed in immunotherapy. This therapy tries to strengthen the body's immune system in such a way that cancer cells are killed by immunological mechanisms. Tumors not only consist of tumor cells, but are surrounded by what is known as the tumor stroma. Immune cells with the potential to attack cancer cells are also found in the tumor stroma. Unfortunately, tumors have developed strategies to block immune cells. Instead of being killed, the tumors benefit from the immune cells because they produce factors that promote tumor growth. Such tumors are unlikely to respond to immunotherapies. Sensitizing tumor cells to immune attack is an important strategy for reversing immunosuppression. However, little is known about the underlying mechanisms of immunosuppression. As part of the FWF project, indoleamine-2,3-dioxygenase-1-positive tumor cells were discovered in intestinal tumors. Indoleamine-2,3-dioxygenase-1 is an enzyme that converts the amino acid tryptophan into the immunosuppressive substance kynurenine. With the help of these cells, the intestinal tumors escape the immune system and are no longer attacked by cytotoxic immune cells. The indoleamine-2,3-dioxygenase-1-positive tumor cells are therefore a possible target for immune-based tumor therapy.