Deadly Stowaways: Seeds of cancer in transplant recipients are traced back to donors

An organ transplant gives many people a second chance at life, but the harsh drugs required for staving off immune rejection of the new tissues seem to hike a recipient’s risk of cancer. For someone desperately in need of a heart or liver, this drawback represents a gamble worth taking.

Scientists initially considered this boost in cancer risk to be the result of a suppressed immune system no longer capable of checking the proliferation of cancer precursor cells already in transplant recipients. That may be only part of the explanation. In the May Nature Medicine, researchers report that the cellular precursors for one type of cancer, Kaposi’s sarcoma, can be transmitted in the form of virally infected donor tissue.

Kaposi’s sarcoma occurs 200 times more frequently in transplant patients with a suppressed immune system than in the overall population. It usually shows up in the skin but can attack internal organs. Scientists generally acknowledge a virus in the herpes family as the cancer’s cause.

The new study establishes that transmission of cancer precursors can occur in a solid-organ transplant, says researcher Mario Luppi of the University of Modena and Reggio Emilia in Modena, Italy. In earlier investigations of leukemia patients who had received bone marrow transplants, other scientists found similar signs of viral transmission, which led to different types of blood cancer.

In the new study, Luppi and his team identified eight people who developed Kaposi’s sarcoma within 4 years of getting a kidney transplant. Of the recipients, six were women who received organs from male cadavers. Scientists found that tumor cells in four of the women contained the telltale Y chromosome that appears only in men, establishing that the troublesome cells hitchhiked in the transplant.

Tumor cells in one of the male transplant recipients also carried genetic markers clearly deriving from his donor.

Past work showed that herpesvirus-8 is present in most Kaposi’s sarcoma patients and some healthy people, says Julio C. Mendez of the Mayo Clinic in Jacksonville, Fla.

“This suggests that in people with a healthy immune system, the virus is kept continually under immune surveillance” by so-called T cells, a situation equivalent to house arrest, says Patrick S. Moore of the University of Pittsburgh Cancer Institute. The new study indicates that when virus-infected cells are “seeded” into a recipient who has a suppressed immune system, these cells are suddenly free to proliferate and become cancerous, he says.

To treat those who develop tumors traceable to donor tissue, Luppi proposes using cancer-checking T cells from the donor.

Another approach to reducing cancer risk for transplant recipients would be to stop transmission of virally infected cells before it happens. “Transplant screening for herpesvirus-8 is justified,” says Moore, whose lab has developed and patented such technologies. Because in the United States, only 3 percent of people harbor herpesvirus-8, eliminating contaminated organs wouldn’t have a major effect on transplant availability, Moore says.

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