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Researchers Discover How Cancer Evades the Immune System

A study on various kinds of cancer, conducted by researchers at the University of Southern California, has brought about the discovery of a new method to identify the genetic changes that enable tumours to evade the body's immune system.

The findings, demonstrated in human breast and colorectal cancers, are significant to the field of medicine because they may lead to the advancement of diagnostic tests and treatment for cancers.

"The implication is that once you know the mechanism by which tumours evade the immune system, you can match that tumour to available therapies," said senior author Dr. Alan L. Epstein, Professor of Pathology at USC's Keck School of Medicine.

"First, we find the genetic changes that allow a tumour to defeat the immune system, then we can apply therapies that compensate for these genetic alterations," added the researcher, whose findings have been published in the journal Cell.

Dr. Epstein and his student Rebecca Sadun used real-time PCR (rtPCR), a high-speed gene amplification technique, to screen tumours to identify 14 pro-immunity genes (downplayed by tumours) and 11 anti-immunity genes (promoted by tumours).

The researchers studied the expression of these genes in five mouse tumour models for breast cancer, leukaemia, colon cancer, lung cancer and renal cell carcinoma. When they compared two of these immune signatures with corresponding human tumours thereafter, they found that the immune signatures of each of the human breast cancer cases nearly matched that of mice.

Dr. Epstein says that all cases showed a suppression of CD83 and CD28, two genes that affect activation of immune cells, and over-production of B7-H4, a gene whose protein product inhibits immune activation.

The human colorectal cancers, however, showed variations in their immune signatures, which researchers saw as an indication of the need to understand the signature for each patient's individual cancer.

"I see it as the beginning stages of personalized medicine, where we develop tactics for treating the unique genetic make-up of a specific tumour. It becomes even more necessary when we look at all the immunotherapies that are becoming available or are beginning to emerge from research," Dr. Epstein said.

He also said that the rtPCR technology allowed for a relatively inexpensive and rapid analysis on equipment available at most medical centres.

"For now, we need to better understand the immune signatures for the most common human cancers in order to identify the most important targets for immunotherapy," he said.


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