Why doesn't every cancer patient respond to immunotherapy? That's the question that researcher Daniel Peeper is looking to answer.
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A group of researchers set out to identify the genes that play a role in immunotherapy resistance. In today's cover story in Cell Reports Medicine, they describe an important factor behind this resistance to therapy and a potential way to counter it. The researchers grew tumour cells in their laboratory and inactivated one gene per cell at a time using the CRISPR/Cas9 technique. Then they treated the tumour cells with T cells or NK cells to analyse which genes were involved in resistance against the immune cells. This led to the discovery of three genes from the same family. The screening led us to an entire gene family, which is a real success. Indeed, when they switched off these genes including RNF31, the tumour cells were destroyed much more efficiently by T cells and NK cells. In addition, they found that inhibiting RNF31 also increased the sensitivity of T cells to tumour cells that were invisible on the surface of immune cells. This so-called bystander effect may amplify the effect of the treatment. Â