Genes May Hold the Key to Immunotherapy Resistance

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.