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Tumors found to rewire immune cells, may lead to new cancer treatments

Reprogrammed macrophages activated genes that promote the formation of blood vessels within tumors.

The Tel Aviv University campus on March 15, 2021. Photo by Eitan Elhadez-Barak/TPS-IL.
The Tel Aviv University campus on March 15, 2021. Photo by Eitan Elhadez-Barak/TPS-IL.

Israeli scientists have discovered how cancerous tumors can exploit a normal function of the immune system, a finding that could eventually lead to new cancer treatments.

A study by researchers at Tel Aviv University focused on macrophages, immune cells that patrol the body and remove dead and damaged cells. This process helps maintain healthy tissue and prevent inflammation.

Scientists have long known that tumors can recruit macrophages to support their growth, but the mechanism by which healthy immune cells are transformed into tumor-supporting cells has remained unclear.

The study, led by Tel Aviv University’s Dr. Merav Cohen and doctoral students Roi Balaban and Ori Moskowitz, found that the process begins when macrophages engulf dead cancer cells. Instead of simply breaking down the cellular debris, the macrophages undergo changes in gene activity that alter their behavior and shift them toward supporting tumor growth.

To observe this process, the researchers developed a technique called Effero-seq, which enabled them to identify macrophages that had consumed dead cancer cells and track how their gene expression changed over time.

Using a melanoma model, the team found that these reprogrammed macrophages activated genes that promote the formation of new blood vessels within tumors. These blood vessels supply tumors with oxygen and nutrients, allowing them to grow more rapidly. At the same time, the macrophages became less responsive to signals that normally trigger immune attacks against cancer cells.

The researchers also analyzed data from patients with uveal melanoma, a rare form of eye cancer. They found that patients whose tumors contained higher numbers of macrophages with this genetic signature generally had lower survival rates, suggesting the mechanism may also play a role in human disease.

According to Cohen, the findings offer new insight into how tumors manipulate the body’s immune defenses.

“The better we understand these mechanisms, the better equipped we will be to develop treatments that block them and restore the immune system’s ability to fight cancer,” Cohen said.

The researchers suggest that future therapies may focus not only on targeting cancer cells directly, but also on preventing immune cells from being reprogrammed to support tumor growth. However, they caution that this approach remains experimental and will require further study before clinical application.

“This research points to a new and promising therapeutic target, one that focuses not only on the cancer cells themselves, but also on the processes that enable them to thrive,” Cohen said.

The findings were published in the peer-reviewed journal Science Immunology.

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