Inhibiting Immune System Activity Slows Growth of Neurofibroma Tumors

Cancer researchers have found that plexiform neurofibroma tumors, complex structures that include many different types of cells including nervous tissue (Schwann cells) and cells from the immune system (mast cells), are susceptible to drugs that inhibit immune system activity.

Plexiform neurofibromas are mostly benign tumors that occur around peripheral nerves and are characteristic of the genetic disease neurofibromatosis-1, which is caused by a dominant mutation in the Nf1 gene. Some 250,000 people in the U.S., Europe, and Japan have this mutation.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA; www.utsouthwestern.edu) created a mouse model for human neurofibromatosis-1 by genetically engineering a line of mice that carried two mutated copies of Nf1 in their Schwann cells.

They reported in the October 31, 2008, issue of the journal Cell that possessing two copies of mutated Nf1 in Schwann cells was not sufficient to trigger tumor growth. Additionally, at least one other cell type, preferably immune system mast cells, had to contain a mutated form of Nf1 for tumor growth to be initiated. Transplantation of bone marrow (the source of mast cells) with two normal Nf1 genes prevented 90% percent of the engineered mice from developing neurofibromas. This finding confirmed that even with two mutated genes in the Schwann cells, a mutated copy of the gene must also be present in other cells.

Treatment of the genetically engineered mice with the drug imatinib (Gleevec), which inhibits the mast cell surface protein c-kit, was shown by positron emission tomography (PET) to lower tumor metabolic activity by about 50%. Tumors that did develop were much smaller than those that grew in placebo-treated mice.

"We found there was a requirement from the immune system to interact with the tumor for the tumor to grow,” said contributing author Dr. Luis Parada, professor of developmental biology at the University of Texas Southwestern Medical Center. "When mast cells are blocked, the tumor cannot grow. It was not the tumor being treated, but its environment. This insight has led to a very promising therapy of a previously untreatable tumor.”

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University of Texas Southwestern Medical Center