Predicting Immunotherapy Response: Research Findings Reveal Key Factors for Successful Outcomes
Every year, groundbreaking advancements are being made in the fight against cancer, with immunotherapy being one of the newest treatment options. However, it's essential to note that not every person and cancer type can benefit from this innovative approach. Researchers from Johns Hopkins University have made a significant breakthrough in pinpointing a specific subset of mutations in cancer tumors that may indicate how receptive they will be to immunotherapy.
These so-called "persistent mutations" are less likely to disappear as the cancer evolves, keeping the tumor visible to the immune system, allowing a more effective response to immunotherapy. The researchers' findings, recently published in Nature Medicine, could help doctors more accurately select individuals for immunotherapy and better predict its outcomes.
Immunotherapy harnesses the body's immune system to combat the disease, boosting its ability to locate and eradicate cancer cells. There are several types of immunotherapy, including immune checkpoint inhibitors, regulatory T-cell therapies, and antibody-drug conjugates. Immunotherapy has shown promising results for treating breast cancer, melanoma, leukemia, and non-small cell lung cancer, with further research underway for its use in prostate, brain, and ovarian cancer.
Historically, doctors have used the total number of mutations in a tumor—known as the tumor mutational burden (TMB)—to estimate how well a tumor may respond to immunotherapy. However, Johns Hopkins' researchers have now identified a subset of persistent mutations within the overall TMB that are less likely to disappear as cancer progresses. These persistent mutations keep the cancer visible to the immune system, allowing for a more significant immune response when undergoing immunotherapy.
"Persistent mutations may render the cancer cells continuously visible to the immune system, eliciting an immune response that 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," said Dr. Valsamo Anagnostou, a senior author of the study and associate professor of oncology at Johns Hopkins.
She added that persistent mutation load could help doctors more accurately select patients for immunotherapy clinical trials or predict patient outcomes with standard immune checkpoint blockade treatment. 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, echoed the potential impact of these findings.
"Persistent mutations and mutation-associated neo-antigens, efficiently presented by the patient's own complement of class I and class II [antigen-presenting cells] and recognized by the patient's own complement of T cells, are likely the most important determinants of an effective anticancer immune response, which is stimulated and amplified by the immunotherapeutic agents currently in use," said Dr. Margolin.
Further research will be needed to fully understand the implications of these findings for how cancer patients are selected for immunotherapy in the future. But with ongoing advances in cancer treatment, the future of oncology looks increasingly bright.
- Researchers from Johns Hopkins University discovered a set of persistent mutations in cancer tumors that might indicate a tumor's receptiveness to immunotherapy, keeping it visible to the immune system for a more effective response.
- Johns Hopkins' researchers have identified a subset of persistent mutations within the overall TMB that could help doctors more accurately select patients for immunotherapy clinical trials or predict patient outcomes with standard immune checkpoint blockade treatment.
- The ongoing research into immunotherapy and its potential use in various medical conditions like breast cancer, melanoma, leukemia, non-small cell lung cancer, and future possibilities in prostate, brain, and ovarian cancer might lead to a brighter future in oncology.
