Researchers have added to evidence that a gene responsible for turning off a cell’s natural ‘suicide’ signals may also be the culprit in making breast cancer and melanoma cells resistant to therapies that use the immune system to fight cancer.

When the gene, called BIRC2, is sent into overdrive, it makes too much, or an «overexpression,» of protein levels. This occurs in about 40% of breast cancers, particularly the more lethal type called triple negative, and it is not known how often the gene is overexpressed in melanomas.

If further studies affirm and refine the new findings, the researchers say, BIRC2 overexpression could be a key marker for immunotherapy resistance, further advancing precision medicine efforts in this area of cancer treatment. A marker of this kind could alert clinicians to the potential need for using drugs that block the gene’s activity in combination with immunotherapy drugs to form a potent cocktail to kill cancer in some treatment-resistant patients.»Cancer cells use many pathways to evade the immune system, so our goal is to find additional drugs in our toolbox to complement the immunotherapy drugs currently in use,» says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Genetic Medicine, Pediatrics, Oncology, Medicine, Radiation Oncology and Biological Chemistry at the Johns Hopkins University School of Medicine, and director of the Vascular Program at the Johns Hopkins Institute for Cell Engineering.

Semenza shared the 2019 Nobel Prize in Physiology or Medicine for the discovery of the gene that guides how cells adapt to low oxygen levels, a condition called hypoxia.

In 2018, Semenza’s team showed that hypoxia essentially molds cancer cells into survival machines. Hypoxia prompts cancer cells to turn on three genes to help them evade the immune system by inactivating either the identification system or the «eat me» signal on immune cells. A cell surface protein called CD47 is the only «don’t eat me» signal that blocks killing of cancer cells by immune cells called macrophages. Other cell surface proteins, PDL1 and CD73, block killing of cancer cells by immune cells called T lymphocytes.

These super-survivor cancer cells could explain, in part, Semenza says, why only 20% to 30% of cancer patients respond to drugs that boost the immune system’s ability to target cancer cells.

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Materials provided by Johns Hopkins Medicine. Note: Content may be edited for style and length.