Exploring Immunotherapy: Scientists Discover Methods to Forecast Results
Every year, the fight against cancer sees advancements in treatment. Immunotherapy, a novel method, leverages the body's immune system to combat the disease. However, not every cancer or individual responds to immunotherapy. Researchers from Johns Hopkins University have identified a specific subset of mutations in cancer tumors that can indicate a tumor's susceptibility to immunotherapy.
The team believes these findings will help doctors identify suitable patients for immunotherapy and even predict treatment outcomes more accurately. Their work was recently published in the journal Nature Medicine.
Immunotherapy boosts the body's immune system, helping it locate and destroy cancer cells. There are various types of immunotherapy, including checkpoint inhibitors and CAR-T cell therapy. Currently, it is a treatment option for cancers such as breast cancer, melanoma, leukemia, and non-small cell lung cancer. Researchers are also exploring its potential for use in cancers like prostate, brain, and ovarian cancer.
According to the study, doctors currently gauge a tumor's responsiveness to immunotherapy using the total number of mutations, known as tumor mutation burden (TMB). However, the Johns Hopkins researchers identified a subset of these mutations, called "persistent mutations," which maintain a tumor's visibility to the immune system. This allows for 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," said Dr. Valsamo Anagnostou, a senior author of the study and an associate professor of oncology at Johns Hopkins. "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."
The team found that persistent mutations 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.
Cancer tumors with persistent mutations often involve alterations in DNA damage response pathways, mismatch repair genes, and frameshift mutations. These mutations can lead to the production of neoantigens, which make the tumors more responsive to immunotherapy, particularly for tumors with microsatellite instability-high (MSI-H) and mismatch repair-deficient (dMMR) phenotypes. While the method poses challenges due to tumor heterogeneity, targeting shared neoantigens offers a promising approach for broader therapeutic applicability.
- The research from Johns Hopkins University has discovered a specific set of mutations in cancer tumors, called "persistent mutations," which can indicate a tumor's susceptibility to immunotherapy.
- These persistent mutations may help doctors more accurately select patients for clinical trials of novel immunotherapies or predict a patient's clinical outcome with standard-of-care immune checkpoint blockade.
- According to the study, cancer tumors with persistent mutations often involve alterations in DNA damage response pathways, mismatch repair genes, and frameshift mutations.
- Targeting shared neoantigens resulting from these persistent mutations offers a promising approach for broader therapeutic applicability in various medical conditions like breast cancer, melanoma, leukemia, and non-small cell lung cancer, as well as potential use in cancers like prostate, brain, and ovarian cancer.
