Predictable Outcomes in Immunotherapy: Scientists Uncover Key Factors
Year after year, advancements are made in the fight against cancer, and the latest addition to the arsenal is immunotherapy.
Immunotherapy, a treatment that harnesses the body's immune system to combat the disease, has been found to be effective for some forms of cancer, but not all. Researchers are tirelessly in search of the factors that determine its success.
Good news comes from Johns Hopkins University in Maryland, where scientists have found a specific subset of mutations within a cancer tumor that suggests how receptive it might be to immunotherapy. This discovery could lead to doctors being able to select patients more accurately for immunotherapy and predict the treatment's outcome more effectively.
Their research was recently published in the journal Nature Medicine.
What is Immunotherapy?
Immunotherapy is a powerful tool utilizing the body's immune system to fight the illness. Often, cancer cells develop mutations that allow them to evade the immune system. Immunotherapy provides a much-needed boost, making it easier for the immune system to track down and destroy cancer cells.
There are several types of immunotherapy, including:
Immunotherapy is currently a treatment option for breast cancer, melanoma, leukemia, and non-small cell lung cancer. Researchers are currently studying its potential as a treatment for other types of cancer, such as prostate cancer, brain cancer, and ovarian cancer.
Examining Mutations
Currently, doctors estimate a tumor's receptiveness to immunotherapy by looking at the total number of mutations in a tumor, known as the tumor mutational burden (TMB). However, Johns Hopkins researchers have discovered a specific subset of mutations within the overall TMB, which they aptly named "persistent mutations." These mutations tend to remain in the cancer cells, making the tumor more visible to the immune system and improving the 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," said Dr. Valsamo Anagnostou, a senior author of the study, associate professor of oncology, and director of the thoracic oncology biorepository at Johns Hopkins.
She added that the number of these persistent mutations better predicts the tumor's response to immune checkpoint blockade compared to the overall TMB.
"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," Anagnostou said.
Looking Towards the Future
When asked how these findings might impact the selection of cancer patients for immunotherapy in the future, Dr. Kim Margolin, a medical oncologist and medical director of the Saint John's Cancer Institute Melanoma Program at Providence Saint John's Health Center, said it is likely that high-throughput, next-generation sequencing techniques will soon be used to study patients' mutational spectrum. This will allow doctors to categorize patients by their likelihood of responding to immunotherapy or receiving benefits from other treatments.
"Ultimately, what starts out as mere prognostic indicators may be pushed to the point of becoming predictive factors that can interact with therapy and disease, and even influence sites of recurrence, where the elements of the immune tumor environment are critical elements," Margolin explained.
- The discovery of a specific subset of mutations, dubbed "persistent mutations," by Johns Hopkins University researchers has the potential to aid doctors in selecting patients for immunotherapy more accurately.
- These "persistent mutations" are found to consistently remain in cancer cells, increasing the visibility of the tumor to the immune system and improving the response to immunotherapy.
- Research findings published in the journal Nature Medicine suggest that the number of persistent mutations better predicts a tumor's response to immune checkpoint blockade compared to the overall tumor mutational burden (TMB).
- With the ability to study patients' mutational spectrum using high-throughput, next-generation sequencing techniques, doctors might soon be able to classify patients by their likelihood of responding to immunotherapy or other treatments, positively impacting the selection of cancer patients for immunotherapy in the future.
