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Study investigates why tumor infiltrating lymphocytes not effective in all metastatic melanoma patie

Genetic variables may make tumor infiltrating lymphocytes ineffective in the treatment of some patients with metastatic melanoma, according to the results from a recent study.

Immune-based therapies have increased the number of people with advanced melanoma who survive longer than five years to 30% or more from 10%, according to Dr. Jeffrey Weber, medical oncologist and the study’s senior investigator.

Many immunotherapies still fail, however, with part of the problem attributed to tumor cells suppressing the T cell populations that enable immunotherapy, said Dr. Weber, the deputy director of the Perlmutter Cancer Center and a professor at NYU Langone in New York.

He added that the factors involved in regulating gene activity tied to T cell function also were likely to play a role in treatment failure.

This study was presented at the annual meeting of the American Society for Clinical Oncology in Chicago on June 4, 2016.

Epigenetic changes, gene activity changes assessed

The current study results are based on an analysis of the genes in 24 melanoma patients. During the investigation, the researchers searched for patterns of changes in the epigenome, or chemical modifications to the DNA code that assist in controlling which genes are turned on and which genes are turned off.

They found more than 60 epigenetic changes as well as 10 changes in gene activity that were most common to people for whom immunotherapy failed. Many of these changes were known from previous research to control the process by which immature cells become either CD4 or CD8 immune T cells. In immunotherapy, both are essential in recognizing and attacking cancer cells, says Dr. Weber, who proposes that these changes lead to T cell malfunction.

“Our research offers key evidence for genetic and epigenetic dysregulation as a reason these powerful immune therapies fail to work for so many people with widespread melanoma,” said Dr. Weber.

Researchers plan to perform additional epigenetic analyses.

“If our research is confirmed, it suggests that by modifying the genetic or epigenetic alterations we have identified, we can potentially turn treatment non-responders into responders and broaden the success that immunotherapies are having against melanoma and other cancers,” said Dr. David Woods, lead investigator on the study.

The proposed corrective actions would have an added advantage in that they could be performed in the patients’ T cells while the cells are grown in the lab and before the cells are injected, presenting a potentially safe and convenient treatment option, explained Dr. Woods.

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