How melanoma resists an immunotherapy drug
October 11, 2016
Medically Reviewed | Last reviewed by an MD Anderson Cancer Center medical professional on October 11, 2016
¡°Loss of interferon-gamma signaling caused by these mutations is the first clearly defined resistance pathway to ipilimumab found in tumor cells,¡± said study leader , M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology. She also is scientific director of MD Anderson¡¯s , part of the , which is designed to accelerate development of life-saving innovations from scientific discoveries.
Interferon gamma is an immune response-stimulating cytokine ¨C a signaling molecule crucial to activating immune cells. In addition, interferon gamma directly attacks tumor cells by connecting to receptors on the cell surface and setting off a chain of events that inhibits cell growth and promotes tumor cell death. It¡¯s this direct cell-killing role that may be blocked by genetic mutations, Sharma said.
The study¡¯s findings open the door to testing an array of interferon gamma genes as a predictor for response to ipilimumab and for exploring new combinations to defeat interferon gamma-related resistance.
Ipilimumab, known commercially as Yervoy, was the first drug to unleash an immune attack on cancer by blocking a protein that acts as a brake on T cells, white blood cells that serve as the adaptive immune system¡¯s guided missiles. The drug was approved in 2011 for metastatic melanoma and is in clinical trials as a single agent or in combination with other drugs in many other types of cancer.
¡°Research has shown that ipilimumab treatment provides a significant survival benefit in about 20 percent of patients with melanoma,¡± Sharma said. ¡°The mechanisms responsible for the lack of clinical response in the majority of patients have remained unknown.¡±
Read more about this study in MD Anderson¡¯s Newsroom.