A technological breakthrough by medical researchers at Tel Aviv University (TAU) enabled the discovery of a cancer mechanism that prevents the immune system from attacking tumors. The researchers were surprised to find that reversing this mechanism stimulates the immune system to fight the cancer cells, even in types of cancer considered resistant to prevailing forms of immunotherapy.
Research in a biomedical lab – illustrative photo. Image credit: CDC
The breakthrough was led by Professor Carmit Levy, Professor Yaron Carmi, and PhD student Avishai Maliah from TAU’s Faculty of Medical & Health Sciences. The paper was published in the journal Nature Communications.
“It all happened by coincidence,” Professor Levy says. “My lab studies both cancer and the effects of ultraviolet (UV) radiation from the sun on our skin and body, both of which are known to suppress the immune system. Cancer suppresses approaching immune cells and solar radiation suppresses the skin’s immune system.
“While, in most cases, we cancer researchers worldwide focus on the tumor and look for mechanisms by which cancer inhibits the immune system, here we proposed a different approach: investigating how UV exposure suppresses the immune system and applying our findings to cancer. The discovery of a mechanism that inhibits the immune system opens new paths for innovative therapies.
“With this idea in mind, I asked my colleague Professor Carmi, a global expert on the immune system, to join the study,” Professor Levy adds. “Avishai Maliah, an MD/PhD candidate in my lab, led the project. The first stage was a comprehensive investigation of changes in the skin induced by exposure to UV, using a mouse model. Avishai examined the behavior of dozens of proteins post-UV exposure, and surprisingly discovered a significant rise in the level of a relatively unexplored protein called Ly6a.
“This unexpected finding led us to investigate further, to understand the protein function and whether it is involved in the immune suppression process.”
“It’s important to understand a basic aspect of the immune system’s function,” Professor Carmi explains. “Our natural immune system is very efficient and very powerful, but it contains quite a few brakes and controls, to prevent overactivity that can cause autoimmune diseases in which the body attacks itself.
“When our skin is exposed to UV radiation from the sun, our immune system responds immediately: blood vessels expand, DNA is repaired wherever possible, and cells with mutations are identified and removed. At the same time, a strong control system with numerous brakes is also activated to prevent overactivity.”
“We found that after exposure to UV radiation, the immune system’s T cells, which play a critical role in fighting cancer, begin to express high levels of the protein Ly6a,” Maliah says. “We suspected that Ly6a serves as a brake through which UV inhibits the immune system, and that by releasing this brake, optimal activation of the immune system might be resumed.”
“We were surprised to discover that this protein, Ly6a, is also overexpressed in cancer tumors, apparently inhibiting T cells,” Professor Levy says. “Having found this in two types of cancer, melanoma skin cancer and colon cancer, we have reason to believe that the same thing happens in other cancers as well. Evidently, we have discovered a general mechanism through which cancer tumors desensitize the immune system.”
“Immunotherapy has revolutionized the treatment of cancer,” Professor Carmi summarizes. “However, about 50% of the patients do not respond to the currently prevailing treatment, the protein PD1. We discovered a new protein, Ly6a, and found that its antibody eradicated tumors in our model animals, even those resistant to PD1 therapy. At present we are working to translate our findings into a drug for human cancer patients, hoping to offer an effective new treatment.”
Source: AFTAU