Link between immune protein and longer survival in melanoma patients

Nov 5 2004

Immune responses to prevent or delay the spread of melanoma, a deadly form of skin cancer, are more likely to prolong survival in patients if their immune cells carry a special kind of marker on the surface, according to a team of researchers at the University of Virginia Health System.

The finding is published in the November 1 issue of the journal Cancer Research.

The researchers correlated the presence or absence of the protein with survival in 52 U.Va. patients with advanced metastatic melanoma who were enrolled in experimental clinical trials over the last decade. They found that survival increased by fifty percent in patients whose T lymphocytes (the immune cells that kill tumors) carried a particular protein, or chemokine receptor, called CXCR3.

Increased survival was seen in patients with Stage III metastatic melanoma, but no increased survival was noticed in patients with Stage IV, stressing the importance of early detection and treatment for melanoma.

"As immunologists continue to target the spread of cancer, this research gives scientists new clues to help develop vaccines that both 'turn-on' cancer-killing immune cells, as well as instruct the cells on how to find tumors. Together, that will improve the efficacy of vaccines against cancer in the future," said the study's principal investigator David W. Mullins, PhD, assistant professor of microbiology and a researcher in the Human Immune Therapy Center (HITC) at the U.Va. Health System.

The idea behind this type of vaccine is to activate an immune response within the body against melanoma. In the past, Mullins explained, physicians have delivered vaccines that can get lost in the circulatory system. But, researchers can now target vaccines to certain lymph nodes in the body that they know will generate T cells with the appropriate chemokine receptor like CXCR3- a 'homing' feature that allows these killer cells to find and eradicate tumors.

"This data may indicate that early melanoma vaccination is essential, and that vaccines inducing specific T cells with tumor-homing ability can make a significant difference in survival," said study co-author Irene Mullins, an instructor in the Department of Health Evaluation Sciences at U.Va.

"With lung disease for example, where surgery may not be an option, vaccines offer a treatment alternative to prolong the lives of patients," David Mullins said. "Something as simple as the induction of a particular chemokine receptor on T cells can translate into enhanced survival, which can be quite profound."

The discovery was made possible because of a unique combination of resources at the U.Va. Health System, including collaboration between laboratory scientists, clinicians and statisticians. David Mullins stressed that the organization of the Human Immune Therapy Center at U.Va. means that research can be brought from the lab to the clinic in a matter of days, rather than months or years. "We are quickly retargeting vaccines at U.Va. to be used in patients, taking advantage of our observations," Mullins said.

Last year, Dr. Craig Slingluff, professor of surgery at U.Va. and director of the HITC, reported that using molecules called peptides to treat melanoma resulted in an immune response from 75 percent of the patients in a phase II clinical trial of a melanoma vaccine. The vaccine was also associated with tumor regression.