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Dr. Kelly Paulson, the first author of the study. (Fred Hutch Photo)

Few advances in cancer treatment have gotten as much attention in the past decade as immunotherapies, therapies that use the immune system to fight the disease.

Various immunotherapies have wiped out disease in terminal patients and have largely enjoyed success as they emerge on the market. But despite those successes, many patients see their cancer return a few months or years after treatment.

In a new study published Monday, scientists unveiled a potential reason for these relapses. Researchers at the Fred Hutchinson Cancer Research Center discovered that relapsed Merkel cell carcinoma, a skin cancer, actually turns off a specific gene that letsT cells find and destroy the cancer, effectively shielding the disease from this immunotherapy treatment.

“It’s absolutely revelatory,” Dr. Aude Chapuis, the senior author of the study, said in a statement. “We didn’t know what was going on with these patients and how their cancer was able to come back. Now we are able to understand what’s going wrong, and that gives us a way to fix it.”

The problem of cancer relapsing after T cell treatment is particularly troublesome for some patients with Merkel cell carcinoma, a rare cancer caused by a common virus. T-cell therapies, which artificially boost a patient’s own immune cells to fight the disease, have proven effective against the cancer — but the disease often returns.

“Twenty percent of Merkel cell patients have an initial response to immunotherapy but then relapse – it’s been unclear why,” Dr. Kelly Paulson said in a statement. Paulson is a senior fellow at Fred Hutch and was the first author of the study.

“Understanding the cause of relapse allows us to design immunotherapies that can get toward long-term tumor control to make cancer a more chronic disease,” she said.

A microscopic image of a tissue sample taken from a patient. Activated T cells (pinks, oranges, red and green) surround and engulf a shrinking Merkel cell carcinoma tumor (light blue). (Fred Hutch Photo)

The patients in the study received checkpoint inhibitor immunotherapy that activates the immune system along with T-cell therapy, where scientists remove the immune cells that are able to recognize and attack cancer and then multiply them. The larger amount of cells are infused back into the patient and are then able to more effectively fight the disease.

The patients studied had seen their cancer be wiped out by the treatment, but their disease returned within a few years. Researchers discovered that the new disease had actually turned off one of the three biological agents that the T-cells targeted. This was highly unusual because the three targets are normally turned on or off as a unit, not individually.

Researchers said the results point towards the need to use multiple treatments at once to fully thwart a patient’s cancer, forestalling a relapse like the ones seen in these patients.

“It’s very obvious we need a multi-pronged approach rather than just one dagger that the cancer can escape,” Chapuis said.

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