Exploring Predictive Factors: Scientists Discover Methods to Forecast Immunotherapy Results
A new study from Johns Hopkins University researchers has shed light on a specific subset of mutations in cancer tumors that could indicate a tumor's susceptibility to immunotherapy.
Each year, scientists strive to develop innovative treatment options for cancer, one of them being immunotherapy. This treatment method leverages the body's immune system to fight the disease. However, it is not effective for every cancer type or individual. Thus, researchers are continually searching for factors that could predict a tumor's response to immunotherapy.
In this study, the research team identified a subset of mutations within a cancer tumor, which they termed "persistent mutations." Unlike other mutations, these mutations do not disappear as the cancer evolves, making the tumor more visible to the immune system. This increased visibility can lead to a better response to immunotherapy.
According to Dr. Valsamo Anagnostou, a senior author of the study and an associate professor of oncology at Johns Hopkins, persistent mutations "may render the cancer cells continuously visible to the immune system, eliciting a sustained immune response." This response is further amplified by immune checkpoint blockade, enhancing the elimination of cancer cells with persistent mutations over time.
Tumor mutation burden (TMB) has been previously used to estimate a tumor's receptiveness to immunotherapy. TMB is the total number of changes in a tumor's genetic material, providing more opportunities for the immune system to identify and attack the tumor. However, the study suggests that persistent mutations more accurately predict a tumor's response to immunotherapy than overall TMB.
The research team believes their findings could help doctors more accurately select patients for immunotherapy and better predict outcomes. Their work was recently published in the journal Nature Medicine.
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 in California, praised the study. She stated that persistent mutations and associated neo-antigens are likely critical determinants of an effective anticancer immune response, which is further activated by immunotherapeutic agents. In the future, high-throughput, next-generation sequencing techniques may be used to categorize patients based on their likelihood of response to immunotherapy.
The study reveals that persistent mutations, a specific subset of mutations in cancer tumors, could hold the key to a tumor's responsiveness to immunotherapy, surpassing the predictive capabilities of overall Tumor Mutation Burden (TMB). Immunotherapy, a type of medical-condition treatment that utilizes the immune system to combat cancer, could benefit significantly from the identification of these persistent mutations, potentially leading to improved patient selection and more accurate outcome predictions.
