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Evaders Lymphoma cells like these can survive chemotherapy by hiding out in the thymus.

After receiving chemotherapy, many cancer patients go into a remission that can last months or years. But in some of those cases, tumors eventually grow back, and when they do, they are frequently resistant to the drugs that initially worked.

Now, in a study of mice with lymphoma, MIT biologists have discovered that a few cancer cells escape chemotherapy by hiding out in the thymus, an organ where immune cells mature. In the thymus, the cancer cells are bathed in growth factors that protect them from the drugs’ effects. These cells are the likely source of new tumors, says study leader Michael Hemann, an assistant professor of biology and a member of the David H. Koch Institute for Integrative Cancer Research.

Successful cancer therapy needs to kill tumor cells and also block pro-survival signals to the cells, he says. “Current cancer therapies fail to target this survival response.”

Hemann and his colleagues treated the mice with doxorubicin, a drug used against a wide range of cancers, including blood cancers. They found that during treatment, cells that line the blood vessels release cytokines, small proteins that influence immune responses and cell development. These cytokines protect immature cells that can develop into different types of blood cells, but tumor cells coöpt the system for their own benefit.

The discovery marks the first time scientists have seen a protective signal evoked by chemotherapy in the area surrounding a tumor, known as the tumor microenvironment. While the MIT researchers observed this protective effect only in the thymus, they believe there may be other protected areas where tumor cells hide, such as bone marrow.

“It’s completely unexpected that drugs would promote a survival response [in cancer cells],” says Hemann. “The impact of local survival factors is generally not considered when administering chemotherapy, let alone the idea that frontline chemotherapy would induce pro-survival signals.”

The researchers plan soon to begin tests, in mice, of drugs that interfere with one of the cytokines that help protect tumor cells. Those cytokine blockers were originally developed to treat arthritis and are now in clinical trials for that use. Such drugs, used in combination with traditional chemotherapy, could thwart the protective effect of cytokines, preventing cancer cells from hiding out and minimizing the risk of relapse.

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Credit: Ed Uthman

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