In this increadible medical breakthrough, the team found that reversing this mechanism can stimulate the immune system to combat cancer cells, even in types of cancer previously deemed resistant to standard immunotherapy.
The research, led by Prof. Carmit Levy, Prof. Yaron Carmi, and PhD student Avishai Maliah from TAU's Faculty of Medical & Health Sciences, was published in the esteemed journal Nature Communications.
Prof. Levy remarked, "This discovery occurred by chance. My lab investigates both cancer and the effects of ultraviolet (UV) radiation, which is known to suppress the immune system. While cancer typically inhibits immune cell activity, we decided to explore how UV exposure affects immune suppression and apply that knowledge to cancer."
Prof. Levy continued, "With this concept in mind, I collaborated with my colleague Prof. Yaron Carmi, an expert in immunology, and our MD/PhD candidate Avishai Maliah led the project. We began by studying the effects of UV on the skin using a mouse model, examining the behaviour of numerous proteins after UV exposure. To our surprise, we found a significant increase in a lesser-known protein called Ly6a, prompting further investigation into its role in immune suppression."
Prof. Carmi elaborated on the immune system's complexities, explaining that while it is highly effective, it also has numerous checks to prevent overactivity that could lead to autoimmune diseases. He noted that UV exposure triggers immediate immune responses, but also activates mechanisms to limit immune activity.
Prof. Levy added, "For years, sunlight's role in managing autoimmune skin diseases has been recognized. Phototherapy uses UV radiation to treat conditions like psoriasis and vitiligo because it suppresses the skin's immune system."
Avishai Maliah shared, "Our findings revealed that T cells, crucial for fighting cancer, expressed elevated levels of Ly6a following UV exposure. We hypothesized that Ly6a acts as a brake, inhibiting immune activity, and that releasing this brake could enhance immune response."
Prof. Levy expressed astonishment upon discovering that Ly6a is also overexpressed in cancer tumours, potentially impeding T cell function. After observing this in melanoma and colon cancer, they suspect it occurs in other cancers as well, indicating a broader mechanism by which tumours desensitize the immune system. Remarkably, when Avishai treated tumours with Ly6a antibodies, significant tumour reduction was observed, even in cases resistant to existing treatments.
This discovery has important implications for immunotherapy, which aims to bolster the immune response against cancer.
Prof. Carmi noted, "While immunotherapy has transformed cancer treatment, about half of patients do not respond to the standard PD1 treatment. Our discovery of the protein Ly6a and its antibody's ability to eliminate tumours, including those resistant to PD1 therapy, presents an exciting avenue for developing new treatments for cancer patients."