Tel Aviv Scientists Discover New Cancer-Fighting Mechanism That Destroys Treatment-Resistant Tumors – by Coincidence

In what they say was a discovery by coincidence, Tel Aviv University researchers uncovered a critical cancer evasion strategy, enabling the immune system to be harnessed against previously resistant tumors. The breakthrough was led by Prof. Carmit Levy, Prof. Yaron Carmi, and PhD student Avishai Maliah from TAU’s Faculty of Medical & Health Sciences. The paper was published in the leading journal Nature Communications.

“It all happened by coincidence,” said Prof. Levy. “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.”

Recognizing the potential significance of this research, Prof. Levy partnered with Prof. Yaron Carmi, a world-leading immunologist. Led by the brilliant Avishai Maliah, their team embarked on a meticulous investigation of UV-induced skin changes in mice. A groundbreaking discovery unfolded: a dramatic increase in the expression of the enigmatic protein Ly6a. Driven by curiosity, we delved into the functional implications of this protein in immune suppression.

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“It’s important to understand a basic aspect of the immune system’s function,” said Prof. Carmi. “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 over activity.”

For centuries, sunlight has been harnessed to alleviate autoimmune skin disorders like psoriasis and vitiligo. Phototherapy, a clinical application of UV radiation, capitalizes on this natural phenomenon by effectively dampening the skin’s excessive immune activity.

A groundbreaking finding revealed that UV radiation triggers a significant upregulation of Ly6a protein in T cells, key players in cancer immunity. The scientists postulated that Ly6a functions as a molecular brake on the immune system, and that by disengaging this brake, robust immune responses could be unleashed.

“We were surprised to discover that this protein, Ly6a, is also overexpressed in cancer tumors – apparently inhibiting T cells,” explains Prof. Levy. “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. Avishai treated cancer with Ly6a antibodies, and amazingly the tumors were significantly reduced. Moreover, cancers resistant to known treatments reacted substantially to Ly6a antibodies.”

The new discovery can have practical implications in immunotherapy – treating cancer by enhancing the response of the immune system, say the researchers.