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New gene targets for Immunotherapy

A new study published in Nature identifies over a hundred genes that may be essential for cancer immunotherapy. These brand new findings could also explain why some tumors respond initially but then stop or do not respond to this kind of therapy at all.

The study was led by Dr. Nicholas Restifo, a senior investigator from the National Cancer Institute in collaboration with Georgetown University, Harvard University and the University of Pennsylvania. The researchers developed a two-pronged CRISPR/Cas9 assay, consisting of human melanoma cells and T-cells, to find out how these cells interact. In order to identify which genes are responsible to cause resistance in T-cells, they »cut out” single genes in the human melanoma cells.

The approach proved successful in finding over 100 genes that may play a role in tumor cells regarding their response to T-cells. Further investigations assessed 36 different cancer types for expression of these genes, using genetic data from almost 11.500 tumors from the Cancer Genome Atlas database. In the end, the researchers were able to single out a subset of 19 genes that were associated with tumor cytolytic activity in patient samples with different kind of tumors. Mutations in these genes proofed also to be more common in patients who did not respond to ipilimumab.

Particularly interesting seems to be a protein called APLNR (the capelin receptor). When this gene was mutated in mice, it clearly reduced the efficacy of immunotherapy.
Screening those mutations in individual patients might help doctors to find the most appropriate treatment for each individual cancer patient.

Patel SJ et al., Nature 2017. doi:10.1038/nature23477



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