Predicting Immunotherapy Responses: Scientists Discover Methods for Forecasting Treatment Success
In the ongoing battle against cancer, immunotherapy is rapidly emerging as a promising treatment option. However, its efficacy varies greatly depending on the individual and the type of cancer. Recently, researchers from Johns Hopkins University have made a significant breakthrough by identifying a specific subset of mutations in cancer tumors that indicate a tumor's receptiveness to immunotherapy.
The scientists' discovery could revolutionize the way doctors select patients for immunotherapy and predict the treatment's outcomes. Their research was recently published in the journal Nature Medicine.
Immunotherapy employs the body's immune system to combat cancer cells. Essentially, the immune system receives a boost, enabling it to find and destroy cancer cells more effectively. While immunotherapy is currently a viable treatment option for breast cancer, melanoma, leukemia, and non-small cell lung cancer, researchers are also investigating its use for other types of cancer, such as prostate, brain, and ovarian cancer.
Typically, cancer cells develop mutations that allow them to evade the immune system. Immunotherapy aims to overcome this by enhancing the immune system's ability to detect and eliminate these cancerous cells. Currently, the total number of mutations in a tumor, known as tumor mutation burden (TMB), is used to assess the tumor's potential response to immunotherapy.
In this study, the researchers focused on a subset of mutations within the overall TMB, which they termed "persistent mutations." These mutations remain present as cancer evolves, keeping the tumor visible to the immune system and enhancing 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. 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," explains Dr. Valsamo Anagnostou, a senior author of the study and an associate professor of oncology at Johns Hopkins.
According to Anagnostou, the number of persistent mutations more accurately identifies tumors that are likely to respond to immune checkpoint blockade compared to the overall tumor mutation burden. This new understanding may help clinicians more accurately select patients for clinical trials of novel immunotherapies or predict patient outcomes with standard-of-care immune checkpoint blockade.
Dr. Kim Margolin, a medical oncologist, has also praised the study's findings. "Persistent mutations and mutation-associated neo-antigens, efficiently presented by the patient's own complement of class I and class II human leukocyte antigens and recognized by the patient's own complement of cytotoxic T-lymphocytes, are likely the most important determinants of an effective anticancer immune response," she says.
While the specific subset of mutations identified by the Johns Hopkins team is not explicitly detailed in the study, their findings strongly suggest that a high-throughput, next-generation sequencing approach could be used to categorize patients by their likelihood of response to immunotherapy in the future. This approach could potentially pave the way for more targeted and effective cancer treatments in the not-too-distant future.
- The scientists' discovery of 'persistent mutations' in cancer tumors could revolutionize the selection of patients for immunotherapy, enabling doctors to predict treatment outcomes more accurately.
- In the journal Nature Medicine, researchers from Johns Hopkins University published a study on 'immunotherapy' and its efficacy, focusing on a subset of mutations called 'persistent mutations.'
- According to Dr. Valsamo Anagnostou, a senior author of the study, the number of 'persistent mutations' more accurately identifies tumors that are likely to respond to immune checkpoint blockade compared to the overall tumor mutation burden.
- The approach of categorizing patients by their likelihood of response to 'immunotherapy' using a high-throughput, next-generation sequencing method, as suggested by the Johns Hopkins study, could pave the way for more targeted and effective cancer treatments in the near future.
