Nature's deep interpretation! How scientists have identified dozens of key genes that help cancer cells evade attack by the host immune system!

September 27, 2020 // -- In a recent study published in the international journal Nature entitled "Functional genomic landscape cancer-intrinsic evasion of killing by T cells", scientists from the University of Toronto and other institutions identified dozens of genes that promote cancer cells to evade the host body's immune system.
researchers say they have mapped genes that help cancer cells avoid being killed by the host immune system, a finding that could provide new ideas for the development of new immunotherapy. Professor Jason Moffat, a
researcher, says different forms of immunotherapy have emerged over the past decade with the aim of becoming potential treatments for cancer effectively, but the reality is that they can only produce a lasting response to a certain number of patients, not all types of tumours.
paper also reveals the genetic make-up of tumors that researchers need to consider to develop new therapies, because mutations in cancer cells potentially contribute to a worsening of the disease's response to treatments, often referred to as cancer-resistant mutations.
It is important to understand at the molecular level how cancer is resistant to immunotherapy so that immunotherapy can be more widely used, and advances in systematic genetic methods can help researchers delve deeper into the genetic and molecular pathways involved in cancer cell resistance, in which the patient's own lethal T-cells can be used to find and destroy cancer, but the resistance of therapy may have prevented its use in most patients, especially solid tumor patients.
this is an ongoing battle between the immune system and cancer, the immune system is trying and killing cancer, and cancer cells are working to avoid this killing effect.
Photo Source: The heterogeneity of National Institutes of Health (NIH) tumors may be more complicated, with genetic mutations in the body and tumor cells in different individual bodies affecting their response to therapy; importantly, researchers need to find not only a gene that regulates immune escape in cancer models, but also genes that manipulate cancer cell behavior in multiple models, which may later be the best therapeutic target. In the
study, researchers looked for genes from six tumor models with different genetic characteristics, including breast, colon, kidney, and skin cancer, that regulate the immune escape of cancer cells, which is like placing cancer cells on a disk and engineering T-cells to kill them, allowing them to turn off each gene in cancer cells one by one using CRISPR gene editing tools and determine the effects.
researchers identified 182 intrinsic immune escape genes in core cancers that are removed to make them more sensitive or to T-cell attacks, and in to-patient cancer cells, all known genes mutate in patients who stop responding to immunotherapy, and convince researchers that these methods are effective.
Many of the genes found have previously been linked by researchers to immune escape; researcher Lawson says this is really exciting because it means adding a lot of biological information to our database; genes involved in cell autophagy are critical to immune escape for cancer cells, which may raise the possibility that cancer cells are susceptible to immunotherapy by targeting autophagy genes.
As the study progressed, the researchers found that removing specific autophagy genes in pairs may make cells resistant to T-cell killer effects, which means that if the tumor already has a mutation in the autophagy gene, combining immunotherapy with drugs that target another autophagy may worsen the patient's condition. 'We found this complete reversal of gene dependence in this study, which we didn't expect at all,' the
researchers said, suggesting that no matter what mutation occurs in the genetic context, it may largely determine whether the introduction of a second mutation has some effect, such as sensitivity to therapy or tolerance.
followed by further research, the researchers will continue to reveal the combined effects of mutations in different types of cancer cells, which may be able to predict which treatment is most effective through the tumor's DNA.
() References: 1. Scientists identify dozens of people of genes allowing cancer cells to the immune systemby University of Toronto (2) Lawson, K.A., Sousa, C.M., Zhang, X. et al. Functional genomic landscape of cancer-intrinsic evasion of killing by T cells. Nature (2020). doi:10.1038/s41586-020-2746-2.