Clinical Topics & News

Genes May Hold the Key to Immunotherapy Resistance

Through gene-editing technology, researchers are steps closer to understanding patient responses to immunotherapies that will result in more effective treatment.


 

Why do some tumors not respond to immunotherapy? Why do some respond at first and then develop resistance? A National Institutes of Health (NIH) study holds some clues to the answer. Using patient samples from The Cancer Genome Atlas, the researchers found > 100 genes that may help T cells destroy tumors.

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The researchers used CRISPR, a gene-editing technology that stops the expression of individual genes in cancer cells. By first “knocking out” every known protein-encoding gene in the human genome and then testing the ability of modified melanoma cells to respond to T cells, they identified “candidate” genes.

A number of the genes identified by the CRISPR screen were associated with cytolytic activity. One, APLNR, which produces a protein called the apelin receptor, had been “suspected to contribute” to cancer development—now, the NIH researchers say, they have the first indication of a role in response to T cells. In some patients who were resistant to immunotherapies, the apelin receptor protein was nonfunctional, indicating that the loss of that protein could limit the response to immunotherapy.

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“Many more genes than we originally expected play a vital role in dictating the success of cancer immunotherapies,” said Shashank Patel, PhD, first author of the study. Their “gene list” could serve as a blueprint to study the emergence of tumor resistance, the researchers say, and lead to more effective treatments.

Source:

NCI study identifies essential genes for cancer immunotherapy [news release] Bethesda, Maryland: National Institutes of Health; August 7, 2017. https://www.nih.gov/news-events/news-releases/nci-study-identifies-essential-genes-cancer-immunotherapy. Accessed August 29, 2017.

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