No wonder immunotherapy fails! There are 182 genes in cancer cells that "trigger" immune escape.

Immunotherapy 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 is that only some patients benefit from immunotherapy, and most do not respond to it.
, finding immune escape mechanisms for cancer cells will lead to greater access to immunotherapy and give more cancer patients hope of survival.
, a team 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-intrinsicsics of killing by T cell 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 are the best therapeutic targets," said Keith A. Lawson of the Donnelly Center for Cell and Biomes research at the University of Toronto and co-lead author of the report. in this study,
" using CRISPR-Cas9 technology, the researchers built 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 petri dish to see which genes were more resistant to T-cells.
found that 182 "core cancer inherent immune escape genes" were missing, making cancer cells more resistant to T-cell attacks.
, many of these genes have not previously been found to be associated with immune escape.
the core genes and pathways that cancer cells inherently evade CTL, the study also upends 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 cells escaping stress, so autophagy genes that target cancer cells may be an important way to increase cancer's sensitivity to immunotherapy.
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.
Moffat said: "We have found a complete reversal of cancer gene dependence, the genetic background, what kind of mutations exist, to a large extent determine whether the introduction of the second mutation will have an impact on the treatment in terms of resistance or sensitivity."
, this 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.
resources: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Scientists identify dozens of genes allowing cancer cells to evade the immune system.