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High-risk neuroblastoma is one of the most aggressive forms of solid tumors affecting children, originating in the nervous system. While a newer class of targeted immunotherapy drugs has improved survival rates, according to the American Cancer Society, cancer can hide from the immune system, causing patients to relapse or develop resistance to treatment. Now, a team of researchers from Penn State College of Medicine has discovered a novel strategy to unmask cancer cells, improving the effectiveness of immunotherapy in cell experiments and mouse models.

In a study published in the journal Autophagy, the researchers found that blocking a single protein, PIK3C3/VPS34, raised levels of GD2, a target molecule for neuroblastoma immunotherapy, on the surface of tumor cells.

Monoclonal antibodies, which are lab-made proteins engineered to recognize and bind to a specific target, attach to GD2 on the surface of tumor cells, marking them for destruction by the patient's own immune cells. Raising the levels of GD2 made the tumor cells in the study easier to detect and more vulnerable to anti-GD2 immunotherapy. It also made the environment around the tumor more hostile to cancer growth.

The findings showed that PIK3C3/VPS34, or VPS34 for short, plays a key role in whether neuroblastoma tumors survive and respond to immunotherapy, said corresponding author Hong-Gang Wang, Lois High Berstler Professor of Pediatrics and professor of cell and biological systems at Penn State College of Medicine.

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