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Number of T-cells predicts response to immunotherapy in melanoma

Study findings may help identify patients who are most likely to respond to a combination of immunotherapy drugs called checkpoint inhibitors to treat melanoma.

By Amy Wallace

July 20 (UPI) -- Researchers at the University of California, San Francisco found the number of immune cells in tumors may predict the efficacy of immunotherapy against melanoma.

The study, published July 20 in the Journal of Clinical Investigation Insight, shows a predictive biomarker can identify which patients would respond better to single immunotherapy drugs or a combination of immunotherapy drugs known as checkpoint inhibitors.

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"Combination immunotherapy is super-expensive and very toxic," Dr. Adil Daud, director of Melanoma Clinical Research at the UCSF Helen Diller Family Comprehensive Cancer Center, said in a press release. "You're putting patients at a lot of extra risk if they don't need it, and you can adjust for that risk by knowing in advance who can benefit."

Researchers analyzed the measures of the abundance of immune cells that infiltrate melanoma tumors, finding that patients with lower levels of immune cells, called T-cells, in their tumors benefited the most from two immunotherapy drugs in combination.

T-cells are immune cells that search the body for signs of infection or disease and are able to recognize them via proteins on their membranes. Normal body cells carry proteins that serve as checkpoints to make them invisible to T-cells, but many cancer cells have now developed the same method of cloaking themselves with the same proteins as normal cells, PD-L1.

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PD-L1 on cancer cells causes T-cells to mistake them for healthy cells, so they do not attack them.

Immunotherapy drugs called checkpoint inhibitors work to identify cancer cells by blocking PD-L1 or PD-1, complementary proteins on T-cells, to allow the T-cells to recognize and kill cancer cells.

"This is clinical research at its best," said Dr. Katy Tsai, a medical oncologist at UCSF. "We have identified something as a predictive biomarker in melanoma, and we're hoping to validate it in other tumor types as well."

There are currently four U.S. Food and Drug Administration approved checkpoint inhibitors on the market -- ipilimumab, nivolumab, pembrolizumab and atezolizumab.

Doctors have used the drugs successfully in many cases but they are only effective for 20 to 40 percent of patients. So, in some cases, more than one drug is used in combination to improve its effectiveness, but toxic side effects increase when they are combined.

In the study, researchers studied tumor samples from 102 melanoma patients and found patients with high levels of exhausted T-cells benefited the most from treatment with a single drug, and women and patients with who had liver metastases had a lower number of immune cells and responded better to combination treatment.

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