October 11, 2012
New Melanoma Treatments Destroy The Skin’s Deadliest Predator
Alan McStravick for redOrbit.com - Your Universe Online
Your skin is responsible for keeping you healthy. It covers your internal organs and actively protects them from injury. The dermal layer also acts as a barrier to germs. Additionally, skin can help to regulate your body temperature, with your skin cells communicating directly with the brain to allow sensations of touch, temperature and pain.
Melanoma, the focus of a new study out of Bonn University, is a cancer that begins in the melanocytes — the cells that produce skin coloring or pigment known as melanin. This skin colorant helps to protect you from harmful UV rays.
If caught early on, melanoma can be treated and cured. Otherwise, it can, and usually does, become particularly dangerous, as it metastasizes early on. Its spread is aided by lymphatic vessels and the bloodstream, allowing for quick spread of small tumors. Current treatment models have utilized the body´s own immune system, in conjunction with other methods. Allowing the immune defense to search out and destroy malignant cells is typically only temporarily effective. The research team, whose findings have been published online in the journal Nature, now knows why this is the case.
According to their research, the inflammatory reaction caused by the treatment allows the tumor cells to temporarily alter their external characteristics thus becoming invisible to defense cells. By recognizing this, combination therapies can be altered and improved, hopefully leading to a drastic decrease in the mortality of melanoma.
This most recent study was derived from a working group under Dr. Thomas TÃ¼ting, Director of the Laboratory for Experimental Dermatology at the Bonn University Hospital. They have specifically investigated the effect of a targeted immune therapy with tumor-specific defense cells.
The trials they used focused on mice that had developed a congenital form of melanoma. While researchers were able to destroy advanced tumors using cytotoxic T-cells, according to Dr. Jennifer Landsberg and Dr. Judith Kohlmeyer, lead authors of the study, ““¦they [melanoma] recover after some time — just as they do in patients in the hospital.”
Marcel Renn, also a lead author of the study went on to say: “They behave like wolves in sheep´s clothing and thus evade detection and destruction by defense cells.”
As mentioned above, the immune system plays an unwitting role in the spread of melanoma. “The immune system is like a double-edged sword,” according to Dr. TÃ¼ting. “It can fight the tumor — but it can also protect it.”
Therapy-resistant melanomas presented a significantly stronger inflammatory reaction with many scavenger cells of the immune system. The study found that messengers released from these immune cells — the tumor necrosis factor-alpha — were able to bring about a change in the character of the melanoma cells directly in the Petri dish in the laboratory. Treated this way, cells were harder to detect by the defense cells.
Recognition of these changes in the tumor tissue is important in that it can lead to the formation of resistance to therapy. “According to more recent discoveries, treatment with inhibitors which prevent signal transmission in tumor cells is also affected by this,” he said.
Viewing the melanoma cells on the molecular level revealed that therapy-resistant tumors had lost the characteristics typical for pigment cells. They actually appeared to demonstrate similar traits with connective tissue cells. “It is possible that melanoma cells undergo this change in character so easily because they originate from the embryonic development of cells in the neural crest which can also form connective tissue and nerve cells,” study coauthor Dr. Michael HÃ¶lzel, of the Institute for Clinical Pharmacology and Clinical Chemistry at the Bonn University Hospital, said in a statement.
The team´s findings, which focused on mice in the laboratory, were also able to be reproduced with human melanoma cells as well as with various associated defense cells in the Petri dish. "Detection by other defense cells which can search out specific genetic changes in the melanoma cells was not affected by this, however," stresses Dr. Thomas WÃ¶lfel, director of a working group involved in the study at the Medical Clinic III of the Mainz University Hospital.
Of particular interest was when inflammation subsided due to the tumor necrosis factor-alpha having no more effect on the human and mouse melanoma cells, those cells regained their pigment-cell characteristics. Once this change occurred, the immune defense cells were able to detect and fight the melanoma once more.
This knowledge can be of specific importance to the development of new treatment strategies. The team believes that defense cells against antigens of various categories and specificity should be used in conjunction with therapeutic inhibition of inflammation that targets the tumor cells.
"Our experimental model system will help us to develop optimally effective combination therapies as rapidly as possible," says Prof. TÃ¼ting. "However, it will still take several years until the clinical application of strategies of this type [is realized]."