Early Immune Response to Cancer Confirmed

Cancer researchers continually search to find the answers to how and why cancer develops. Recognizing the positive link between the earlier detection of cancer and a patient’s chance for cure, the focus on finding the earliest signs of cancer remains strong.

Dr. Michael Girardi, Associate Professor of Dermatology and Associate Clinical Director of the Immunology and Immunotherapy Research Program at Yale Cancer Center, has narrowed his research priorities at Yale to investigate the relationship between the immune system and cancer. Over the last decade, Dr. Girardi and his research team have made several important discoveries to aid our understanding of the role our immune system plays in cancer. Most recently, their research narrowed in on the correlation between damaged cells and cancer development.

The human body uses a process called immunosurveillance to continually monitor, detect, and destroy malignant cells. While immunosurveillance has been commonly accepted, Dr. Girardi analyzed the process more closely to determine if there were very early signs of damaged cells that could be recognized by the immune system before further developing.

In collaboration with colleagues at the King’s College School of Medicine in London, Dr. Girardi’s team studied how the immune system responds to epithelial cells displaying Rae-1, a marker of stress and inflammation. Such markers are considered very early cellular flags for tumor development.

“We recognize that the battle against cancer is more easily won and the odds are stacked in our favor when we can identify responses to the earliest signs of the disease,” Dr. Girardi explained. “By identifying how the immune system reacts to the first cellular flags for the disease we can discover new ways to suppress the development of cancer.”

The expression of Rae-1 molecules triggers an immune system response and reorganization of dendritic cells, T cells, and natural killer T cells, all of which are known to help destroy malignant cells. By studying the immune response to determine the chain of events once Rae-1 molecules have been flagged, researchers found that the body’s immune system does immediately respond to destroy the damaged cells. Unfortunately, the research also revealed that the molecules had the ability to manipulate our body’s response and in some situations avoid destruction by the immune response.

“Our findings confirm our body’s natural reaction and immune response to damaged cells. While we do not know how often our immune system is activated against cellular changes, the potential that our immune system continually battles early cellular signs of cancer is clear,” Dr. Girardi explained.

Because epithelial tissues are a component of several of the body’s organs, including the skin, lungs, colon, prostate, bladder, and cervix, Dr. Girardi’s work will have implications in the fight against many types of cancer. The next step will be to determine how to easily identify the early flags found in immunosurveillance to detect cancers at their earliest point and to customize immunotherapies to combat the cancer’s development.

The results of Dr. Girardi’s collaborative study will have a permanent impact on the field of cancer research. In humans, there is a whole family of analogues to Rae-1, such as MICA and MICB. “Our findings confirm the role of the immune system in earliest signs of cancer and will open the door to new methods of detection and treatment by targeting MICA and MICB genetic variations,” Dr. Girardi said.

This article was submitted by Justin Fansler on July 9, 2011.