Newly discovered gene involved in response to cancer immunotherapy
Researchers at IGP have identified a gene that influences the efficacy of immunotherapy for the cancer type neuroblastoma. This is shown in a study performed in collaboration with research groups in Sweden, Spain and Germany and recently published in Journal of Clinical Investigation.
The cancer type neuroblastoma almost exclusively affects children and there are different types where the high-risk variant is very aggressive. Despite improved survival rates over the years, new and more precise therapies are needed to improve the quality-of-life in patients.
A recently developed way to treat cancer is a kind of immunotherapy where drugs are used to target the ‘brakes’ that are used by cancer cells to avoid being attacked by the immune system. However, high-risk neuroblastoma patients respond poorly to these drugs, likely due to resistance mechanisms in the cancer cells.
In the current study, the researchers identified a gene that is involved in the resistance to this kind of immunotherapy.
“We analysed the whole genome of neuroblastoma cells and employed the ‘genetic scissors’ to excise different parts of the DNA. We found that when the gene H2AFY was removed from cultivated neuroblastoma cells, immune cells could work much more efficiently against them in the presence of immunotherapy,” says Divya Nagarajan, researcher in Yumeng Mao’s research group at IGP and first author of the study.
The function of the protein encoded by H2AFY is not yet understood and no one has shown its relevance in high-risk neuroblastoma. The researchers therefore studied the gene in more detail, e.g. by examining its activity in datasets from children with neuroblastoma to test its relevance in patients.
“These efforts revealed that the H2AFY protein functions as a key regulator of the epigenetic states in neuroblastoma cells, i.e. the chemical modifications of the genome that control which genes are active in these cells. This highlights a vital intersection between epigenetics and cancer immunogenicity, which may also have implications for other cancers and is something that we intend to carefully investigate in the next few years,” says Yumeng Mao, who has led the study.
In the study, the researchers also discovered other genes with a potential role in resistance against immunotherapy for high-risk neuroblastoma. With the current results and future analyses of the identified genes, the researchers wish they can contribute to improved treatments and offer hope to affected patients.