Aggressive and highly mutated cancers are involved in an “evolutionary arms race” with the immune system, recent research suggests.
Throat and stomach cancers with failures in their DNA repair systems accumulate a large number of genetic mutations that make them resistant to treatments such as chemotherapy.
But these numerous mutations mean that they seem foreign to the immune system, leaving them vulnerable to attack and susceptible to new immunotherapies.
Scientists at the Cancer Research Institute, London (ICR), discovered that these “hypermutant” tumors rapidly evolve strategies to disguise the immune system and evade the attack.
They hope that in the future, the findings may help optimize treatment with immunotherapy and other medications such as chemotherapy.
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The study, published in Nature Communications, was funded by Cancer Research UK and Schottlander Research Charitable Trust.
Dr. Marco Gerlinger, Team Leader in Translational Oncogenomics at the ICR, said: “Our new study has shown that in highly mutated tumors, cancer and the immune system participate in an evolutionary arms race in which they continually find new ways of flank each other. ” .
“Seeing how hypermutated tumors and immune cells co-evolve in such detail has shown that the immune system can keep up with changes in cancer, where current cancer therapies can become resistant, and that we could use immunotherapies to Change the balance of these race arms, prolonging the life of patients.
“Next, we plan to study the evolutionary link between hypermutant tumors and the immune system as part of a new clinical trial that analyzes the possible benefit of immunotherapy in bowel cancer.”
Find failures in hypermutant stomach tumors
In the new study, the researchers analyzed the genetic picture of four tumors of the stomach and esophagus that failed in one or more important DNA repair genes.
They analyzed the genetic makeup of seven different areas of each patient’s tumor and at the sites where their cancer had spread.
According to the research, hypermutant stomach tumors had surprisingly high levels of genetic variation, with an average of almost 2,000 different genetic defects.
This is much higher than the 436 failures found in skin cancer, the next most highly mutated type of cancer analyzed in the study.
Extreme heterogeneity, large trunks and parallel evolution in gastric cancer MSI. Our study in @NatureComms https://t.co/INefeLtlno Along with high sensitivity to immunotherapy, it suggests that mutational heterogeneity does not prevent immune recognition when the trunks are large pic.twitter.com/Bz54JJm6N4
– Marco Gerlinger (@MarcoGerlinger) January 16, 2020
Different areas of the same tumor showed extreme variation in their mutations, allowing rapid Darwinian evolution.
The researchers found that the two stomach and throat tumors with the highest level of immune cell infiltration had developed several mutations that allowed them to evade the immune attack.
These mutations occurred in genes that normally help immune cells recognize and attack cancer cells.
When genes do not work normally, the immune system cannot detect cancer cells despite their large number of mutations.
Professor Paul Workman, executive director of ICR, said: “The evolution of cancer is the biggest challenge in cancer research and treatment today, and deepening our understanding of how tumors evolve in response to treatment is absolutely key to find ways to overcome drug resistance. “
“This fascinating new study shows how cancers can evolve in conjunction with the immune system, and each responds to changes in the other.
“Without treatment, cancers will be destined to win this evolutionary arms race, but we can tip the balance in favor of the immune system through the carefully designed use of immunotherapy.”
How does radiation kill cancer if it causes cancer?
Question from: Odysseus Ray Lopez, USA UU.
It’s more like the way weapons can be used to commit a crime or stop it. Radiation causes cancer because its high-energy photons can cause breaks in the DNA strands in your cells. Cells can repair this damage to some extent, but sometimes the repair is not perfect and leaves some defective genes. If the rupture affects one of the many tumor suppressor genes in your DNA, that cell can become cancerous. But cancer cells are also more vulnerable to radiation than ordinary cells. Part of what turns them into cancer cells is their ability to divide rapidly and this usually means that some of the mechanisms of “spelling correction” of DNA are disabled.
So when a cancer cell suffers a break in a DNA chain, it is less likely to repair it correctly. Depending on where the break occurs, it could kill the cell directly or cause it to reproduce more slowly. Radiation therapy uses a focused beam that points only to the part of the body with the tumor, and the dose is carefully calculated to cause minimal collateral damage to healthy cells. Even so, radiation therapy increases the chances of developing a second cancer very little.