A chance discovery in a Tel Aviv University laboratory has found a mechanism which prevents the immune system from attacking cancer tumours. As a result, the researchers have found that reversing this mechanism stimulates the immune system to fight the cancer cells — even in types of cancer previously considered resistant to current forms of immunotherapy.
The three scientists working on the groundbreaking discovery are professors Carmit Levy and Yaron Carmi, together with Ph.D student Avishai Maliah from the university’s faculty of medical and health sciences.
Professor Levy said: “It all happened by coincidence. 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, cancer researchers worldwide focus on the tumour 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.”
Professor Levy added: “With this idea in mind, I asked my colleague Prof. Yaron Carmi, a global expert on the immune system, to join the study.
“Avishai Maliah, a Ph.D 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 behaviour 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.”
Avishai Maliah noted: “We found that after exposure to UV radiation, the immune system’s T cells — that play a critical role in fighting cancer — begin to express high levels of the protein Ly6a. 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.”
Once the trio had isolated the Ly6a protein, they used it to treat two kinds of cancer tumours in mice — and “amazingly the tumours were significantly reduced”. They also discovered that cancers resistant to known treatments reacted well to Ly6a antibodies. Now the Tel Aviv scientists say that their new discovery can have practical implications in immunotherapy – treating cancer by enhancing the response of the immune system.
Professor Levy said: “Evidently, we have discovered a general mechanism through which cancer tumours desensitise the immune system.”
Prof. Carmi added: “Immunotherapy has revolutionised the treatment of cancer. However, about 50 per cent 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 tumours 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.”
The Israeli discovery has been published in detail in the prestigious journal Nature Communications.
