Predicting Treatment Success: Scientists Discover Strategies to Foresee Immunotherapy Results
Every year, scientists innovate new treatments to combat cancer. One of the latest is immunotherapy, which uses your body's immune system to battle the disease. However, immunotherapy doesn’t work for everyone or every type of cancer. Researchers are constantly seeking the reasons behind this, and currently, a team from Johns Hopkins University thinks they have found an answer.
They've identified a specific subset of mutations within a cancer tumor that determine its receptiveness to immunotherapy. These persistent mutations, as they call them, remain stable and visible to the immune system, enhancing the response to immunotherapy.
Typically, doctors analyze the total number of mutations in a tumor, known as the tumor mutation burden (TMB), to predict the tumor's response to immunotherapy. According to Dr. Valsamo Anagnostou, a senior author of the study and an associate professor of oncology at Johns Hopkins, a large number of mutations in cancer cells renders them “foreign” to the immune system, leading to an immune response, particularly when combined with immunotherapy.
Persistent mutations are always present in cancer cells, and they help keep the cancer visible to the immune system. This, in turn, leads to a more significant immune response that is augmented in the context of immune checkpoint blockade, resulting in sustained immunologic tumor control. Furthermore, the number of persistent mutations more accurately indicates the likelihood of a patient responding to immune checkpoint blockade compared to the overall TMB.
Dr. Kim Margolin, a medical oncologist, states that this study provides a fresh perspective on the importance of persistent mutations and mutation-associated neo-antigens, which are efficiently presented by the patient's own complement of class I and class II HLA. These elements, she adds, are likely the most important determinants of an effective anticancer immune response that is stimulated and amplified by immunotherapeutic agents currently in use.
In the future, doctors may use high-throughput, next-generation sequencing techniques to study patients' mutational spectrum, categorize patients by their likelihood of response to immunotherapy, or predict a patient's clinical outcome with standard-of-care immune checkpoint blockade. Future research may even push these prognostic indicators to become predictive factors that can interact with therapy and disease dynamics.
- The persistence of specific mutations within cancer tumors may influence their receptiveness to immunotherapy, as these mutations keep the cancer visible to the immune system, enhancing the response.
- A large number of mutations in cancer cells, known as the tumor mutation burden (TMB), can make the cancer cells "foreign" to the immune system, leading to an immune response that can be further boosted with immunotherapy.
- In the future, doctors may utilize high-throughput, next-generation sequencing techniques to analyze a patient's mutational spectrum, potentially enabling them to predict a patient's response to immunotherapy or even interact with therapy and disease dynamics.
