There are 182 genes in cancer cells that "trigger" immune escape

is known as the "third revolution" in cancer treatment by mobilizing cancer patients' own immune systems and enhancing the function of immune cells. The problem, however, is that only some patients benefit from immunotherapy, and most do not respond to it. Therefore, finding the immune escape mechanism of cancer cells will promote the further popularization of immunotherapy and give more cancer patients hope of survival.Recently, a team of researchers led by Professor Jason Moffat of the Donnelly Center for Cell and Biomeanor Studies at the University of Toronto published a paper in Nature entitled Fusion Genomic Landscape of cancer-intrinsic Evasion of killing by T cells Using the gene editing tool CRISPR to breakthroughly identify the immune escape genes inherent in 182 cancers, the paper maps the genes of cancer cells fleeing immune system damage, paving the way for the effective application of immunotherapy in different types of patients and cancers."It's important to find not only genes that regulate immune escape in a cancer model, but also genes that manipulate cancer cells in multiple cancer models, which will be the best therapeutic target," said Keith A. Lawson of the Donnelly Center for Cell and Biomeanor Research at the University of Toronto and co-lead author of the report.For the study, the researchers used CRISPR-Cas9 technology to build a wizard RNA (gRNA) library of genes capable of knocking out 19,069 encoded proteins, then knocking out genes that encode proteins from six different cancer cell lineages from breast, colon, kidney and skin cancers, and putting those cancer cells in a culture dish with lethal T-cells (CTL) to see which genes were more resistant to T-cell attacks.It was found that 182 "core cancer inherent immune escape genes" were missing, making cancer cells more resistant to T-cell attacks. More importantly, many of these genes have not previously been found to be associated with immune escape.In addition, the study has upended some of the perceptions of cancer cells. Autophagy is the process by which cells accelerate the recycling of their ingredients to reduce post-stress damage, and previous studies have shown that genes associated with autophagy are key to cell escape stress, so autophagy genes that target cancer cells may be an important means of increasing cancer's sensitivity to immunotherapy. In the study, however, the researchers found that the removal of certain autophagy genes in pairs made cells resistant to T-cell killing.That is, if the tumor already contains mutations in one autophagy gene, then a combination of immunotherapy and a drug that targets another autophagy gene will worsen the patient's condition."We found that the complete reversal of cancer gene dependence, the genetic background, and what mutations exist, largely determines whether the introduction of the second mutation has an impact on treatment in terms of resistance or sensitivity," Moffat said. In, the study expands understanding of the genetic pathways associated with the immune escape mechanisms of cancer cells and is important for the development of new cancer immunotherapy.
(Biological Exploration)Resources:1. Functional genomic landscape of cancer-intrinsic evasion of killing by T cells2. Scientists identify dozens of genes allowing cancer cells to evade the immune system