Investigators Discover Strategies to Forecast Immunotherapy Success
Yearly, researchers are coming up with novel treatment options to conquer cancer. One of the latest methods is immunotherapy. But it's not a cure-all; not every individual or cancer type responds to immunotherapy. That's why scientists are persistently investigating what factors might make cancers immune to immunotherapy.
Recently, researchers from Johns Hopkins University have pinpointed a specific subset of mutations in cancer tumors, dubbed "persistent mutations," which hint at a cancer's acceptability to immunotherapy. This discovery can help doctors more accurately select individuals for immunotherapy and predict treatment outcomes. Their study was published in the journal Nature Medicine.
What is immunotherapy?
Immunotherapy is a cancer treatment method that boosts the body's immune system to fight the disease. Usually, cancer cells develop mutations, hiding them from the body's immune system. But immunotherapy strengthens the immune system, making it easier to spot and destroy those mutated cells. There are different types of immunotherapies, such as checkpoint inhibitors, CAR-T cell therapy, and cancer vaccines.
Immunotherapy is currently a treatment option for cancers like breast cancer, melanoma, leukemia, and non-small cell lung cancer. Researchers are also investigating its use in treating other cancer types, such as prostate cancer, brain cancer, and ovarian cancer.
The Importance of Persistent Mutations
Currently, doctors use the total number of mutations in a tumor—called the tumor mutation burden (TMB)—to try to understand how well a tumor will respond to immunotherapy. However, the researchers found that a specific subset of these mutations, persistent mutations, is less likely to disappear as cancer evolves. This allows the cancer tumor to remain visible to the body's immune system, contributing to a better response to immunotherapy.
"Persistent mutations are always there in cancer cells and these mutations may render the cancer cells continuously visible to the immune system, eliciting an immune response that is augmented in the context of immune checkpoint blockade," said Dr. Valsamo Anagnostou, a senior author of the study and an associate professor of oncology at Johns Hopkins. "This response is sustained over time, resulting in long-term immunologic tumor control and survival."
The number of persistent mutations is a more accurate indicator of how likely tumors are to respond to immune checkpoint blockade than overall TMB. Persistent mutation load may help clinicians select patients for clinical trials of novel immunotherapies or predict patient outcomes with standard-of-care immune checkpoint blockade.
A Step Forward in Cancer Treatment
This discovery highlights the potential for more personalized immunotherapy treatments based on a cancer patient's genetic profile. “It was refreshing to see this incredible article demonstrating that a highly-respective collaborative group has gone way beyond the simple concept of tumor mutation burden, and to define persistent mutations, loss of mutation-containing sequences, and in a new light,” commented Dr. Kim Margolin, a medical oncologist at Providence Saint John’s Health Center in California.
In the future, high-throughput sequencing techniques may allow doctors to categorize patients based on their likelihood of responding to immunotherapy. Ultimately, these findings could pave the way for more effective and personalized cancer treatments.
- Immunotherapy, a cancer treatment method, strengthens the body's immune system to fight the disease, allowing it to spot and destroy mutated cancer cells.
- The study published in 'Nature Medicine' by researchers from Johns Hopkins University has identified a specific set of mutations, called "persistent mutations," in cancer tumors, which are less likely to disappear as cancer evolves and can make a cancer tumor more visible to the immune system.
- Persistent mutation load is a more accurate indicator of how likely tumors are to respond to immune checkpoint blockade than overall tumor mutation burden, which may help clinicians select patients for clinical trials of novel immunotherapies or predict patient outcomes with standard-of-care immune checkpoint blockade.
- This discovery has the potential for more personalized immunotherapy treatments based on a cancer patient's genetic profile, paving the way for more effective and targeted cancer treatments in the future.
