Exploration of Immunotherapy: Scientists Determining Potential Methods to Forecast Results
Each year, scientists fossick for new ways to fight the devil known as cancer. One method gaining traction is immunotherapy, which revs up the body's immune system to obliterate cancer cells.
But it's not a cure-all – immunotherapy doesn't work for everyone or every form of cancer. Teams of researchers continue to scourthe earth for the reasons why some tumors eschew immunotherapy's mighty punch.
Now, a crack squad of researchers from Johns Hopkins University claim they've wrangled a particular clutch of mutations within a cancer tumor that serves as a harbinger of how amenable it is to immunotherapy.
They believe their findings will aid doctors in more accurately pinpointing individuals for immunotherapy, and better anticipating outcomes from treatment. Their work was recently published in Nature Medicine.
What's the scoop on immunotherapy?
Immunotherapy is a dodgem car that harnesses the body's immune system to wallop the disease. Typically, cancer cells sport mutations that allow them to stay concealed from the immune system. Immunotherapy pumps up the body's immune system to better spot and dismantle these pesky cells.
There are several different kinds of immunotherapy, including:
- Checkpoint inhibitors
- T-cell transfer therapy
- Tumor vaccines
Currently, immunotherapy is offered as a treatment option for breast cancer, melanoma, leukemia, and non-small cell lung cancer. Scientists are also investigating its use against other forms of cancer, such as prostate cancer, brain cancer, and ovarian cancer.
Peering into mutations
According to the study's researchers, doctors currently gauge a tumor's susceptibility to immunotherapy by crunching the total number of mutations it possesses – known as its tumor mutation burden (TMB) – in the hopes of discerning how it'll react.
"Tumor mutation burden is the number of changes in the genetic material, particularly in the DNA sequence of cancer cells, known as mutations," said one of the senior authors, Dr. Valsamo Anagnostou, an associate professor of oncology at Johns Hopkins and director of the thoracic oncology biorepository.
"A large number of mutations in cancer cells clearly distinguish them from normal cells – in other words, render them 'foreign' to the immune system and as such give more opportunities for the immune system to identify and attack the tumor," she explained. "This is clinically translated into longer clinical outcomes with immunotherapy for some tumors that harbor a high tumor mutation burden."
Sustaining mutations
In this study, Anagnostou and her team plucked a specific subset of persistent mutations from the overall TMB that are less likely to vanish as cancer morphs. This means the cancer tumor remains visible to the body's immune system, enhancing its 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. This response is augmented in the context of immune checkpoint blockade and the immune system continues to eliminate cancer cells harboring these persistent mutations over time, resulting in sustained immunologic tumor control and long survival," said Anagnostou.
"Persistent mutation load may help clinicians more accurately select patients for clinical trials of novel immunotherapies or predict a patient's clinical outcome with standard-of-care immune checkpoint blockade," she added.
Immunotherapy is a medical-condition treatment that utilizes the system to combat cancer by enhancing the immune system's ability to detect and destroy cancer cells.
Doctors determine a tumor's response to immunotherapy based on its tumor mutation burden (TMB), which is the total number of changes in the genetic material of cancer cells.
The study by Johns Hopkins University researchers has identified a specific subset of persistent mutations within a cancer tumor, which are less likely to disappear as cancer evolves, thus making the tumor more visible to the immune system and improving its response to immunotherapy.
The discovery of these persistent mutations may aid clinicians in selecting appropriate patients for immunotherapy clinical trials or predicting a patient's outcome with standard immunotherapy treatments.
