Immunotherapy Outcomes Prediction: Scientists Find Strategies to Forecast Efficiency
Every year, innovative cancer treatments are being developed, and one of the latest is immunotherapy – a treatment option that leverages the body's immune system to fight the disease. While it's effective for some people and certain types of cancer, immunotherapy doesn't work for everyone, and researchers are looking for answers as to why that is.
Johns Hopkins University researchers have recently made a breakthrough in this area, identifying a specific subset of mutations in a cancer tumor that hints at its receptiveness to immunotherapy. They believe this discovery will help doctors select patients more accurately for immunotherapy and better predict treatment outcomes. Their findings were recently published in the journal Nature Medicine.
What is Immunotherapy?
Immunotherapy uses the immune system to combat diseases like cancer. Typically, cancer cells have mutations that allow them to hide from the immune system. Immunotherapy provides a boost, making it easier for the immune system to find and eliminate cancer cells. There are various types of immunotherapy, including:
- Checkpoint inhibitors
- CTLA-4 inhibitors
- PD-1/PD-L1 inhibitors
- Adoptive cell therapy (ACT)
Immunotherapy is currently used as a treatment for cancers such as breast cancer, melanoma, leukemia, and non-small cell lung cancer. Researchers are exploring its potential for use in other forms of cancer, such as prostate cancer, brain cancer, and ovarian cancer.
Examining Mutations
Doctors currently use the total number of mutations in a tumor (called the tumor mutation burden - TMB) to determine how well the tumor will respond to immunotherapy. Researchers from Johns Hopkins have discovered a specific subset of mutations within the overall TMB called "persistent mutations." Persistent mutations don't disappear as the cancer evolves, making the cancer 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 and an associate professor at Johns Hopkins. "This response is augmented in the context of immune checkpoint blockade, resulting in sustained immunologic tumor control and long survival."
The researchers believe that the number of persistent mutations is a better predictor of a tumor's responsiveness to immune checkpoint blockade compared to the overall tumor mutation burden. They hope this discovery will 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.
Hinting at the Future
Dr. Kim Margolin, a medical oncologist, spoke about the study and its potential impact on how cancer patients are selected for immunotherapy in the future. She suggested that in the not-too-distant future, high-throughput, next-generation sequencing techniques will be used to study patients' mutational spectrum, allowing doctors to categorize patients by their likelihood of response to immunotherapy. Margolin also mentioned that persistent mutations and mutation-associated neo-antigens are likely the most important determinants of an effective anticancer immune response.
As research continues, it's expected that immunotherapy will play an increasingly important role in the treatment of various types of cancer, ultimately becoming a standard part of care for many patients.
- The scientific community is eagerly examining the 'persistent mutations' discovered by Johns Hopkins University researchers, as they may serve as a better indicator for a cancer tumor's receptiveness to immunotherapy.
- In the future, innovative medical-health techniques like high-throughput, next-generation sequencing may help doctors identify 'persistent mutations' in cancer patients, allowing them to accurately categorize patients by their likelihood of responding to immunotherapy.
- As science advances, immunotherapy, with its potential to leverage the immune system to combat diseases like cancer, is anticipated to become a standard part of care for a significantly larger number of medical-conditions, including but not limited to breast cancer, melanoma, leukemia, and non-small cell lung cancer.
