One of the fundamental traits of a tumor - how it avoids the immune system - might become its greatest vulnerability, according to researchers from the University of Southern California. Their findings, demonstrated in human breast and colorectal cancers, indicate that a technique for determining a tumor's "immune signature," could be useful for diagnosing and treating specific cancers.
In the July 1 issue of Clinical Cancer Research, a publication of the American Association for Cancer Research, the researchers describe a means for determining which genes have been altered in a tumor to allow it to evade the body's natural defenses. In time, the researchers believe such analysis could become a standard practice in cancer diagnosis and treatment.
"The implication is that once you know the mechanism by which tumors evade the immune system, you can match that tumor to available therapies," said senior author Alan L.Epstein, M.D., Ph.D., professor of Pathology at USC's Keck School of Medicine. "First, we find the genetic changes that allow a tumor to defeat the immune system, then we can apply therapies that compensate for these genetic alterations."
According to Epstein, tumors are notorious for demonstrating a broad array of genetic and biological variations. Their differences vary widely between cancer types, even between subcategories within a particular type of cancer. However, while the genetic variations that comprise an immune signature are complex, the researchers discovered that a small subset of genes is integral in explaining immunological behavior.
Using real-time PCR (rtPCR), a high-speed gene amplification technique, Epstein and his M.D./ Ph.D. student, Rebecca Sadun, screened tumors to identify 14 pro-immunity genes, which tumors downplay, and 11 key anti-immunity genes, which tumors promote. They studied the expression of these genes in five mouse tumor models for breast cancer, leukemia, colon cancer, lung cancer and renal cell carcinoma. They then compared two of these immune signatures with corresponding human tumors, eight cases of human ductal carcinoma and 11 cases of colorectal cancer.