Researchers at Tel Aviv University have uncovered a cancer mechanism that prevents the immune system from attacking tumors, a breakthrough that could pave the way for more effective immunotherapies, according to a paper published late September.
The discovery, led by Prof. Carmit Levy, Prof. Yaron Carmi, and PhD student Avishai Maliah, was published in the peer-reviewed academic journal Nature Communications and discussed that reversing the newly discovered mechanism stimulates the immune system to target cancer cells, even in types of cancer that tend to be more resistant to existing therapies.
According to the researchers, the breakthrough emerged by chance while studying both cancer and the effects of ultraviolet (UV) radiation on the immune system. "We proposed a different approach: investigating how UV exposure suppresses the immune system and applying our findings to cancer," Prof. Levy explained.
The researchers discovered that UV exposure caused a significant increase in the expression of a protein associated with immune response, which was initially identified in the skin after UV exposure. This led them to investigate its role in cancer.
Avishai Maliah, who led the project, found that the protein was overexpressed in cancerous tumors, including melanoma and colon cancer, and likely served as a "brake" to inhibit T cells—immune cells that play a critical role in fighting cancer. "We suspected that [the protein] 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," Maliah said.
Protein to enhance immunotherapy
Prof. Levy and the team’s hypothesis was seemingly confirmed, according to them, when treatment with antibodies relating to the protein led to substantial tumor shrinkage in animal models, even in cases where the cancers had been resistant to other forms of immunotherapy.
Prof. Levy remarked, "We were surprised to discover that this protein, Ly6a, is also overexpressed in cancer tumors—apparently inhibiting T cells." Their findings suggest that the protein could be a key player in how tumors affect the immune system.
The breakthrough has significant implications for immunotherapy, "Immunotherapy has revolutionized the treatment of cancer. However, about 50% of patients do not respond to the currently prevailing treatment," Prof. Carmi explained. "We discovered a new protein, and found that its antibody eradicated tumors in our model animals."
The team is working to translate their findings into a potential treatment for human cancer patients, with hopes of offering an innovative treatment option for those who currently have limited responses to existing therapies.