Predicting Immunotherapy Success: Researchers Pioneer Methods for Forecasting Treatment Results
Tackling Cancer with Immunotherapy: It's Not One-Size-Fits-All
The battle against cancer takes a new front with immunotherapy, a treatment that harnesses the power of our immune system to eradicate the disease. However, this powerful tool doesn't work for everyone or every type of cancer. Researchers at Johns Hopkins University believe they've found the answer in the form of a specific subset of mutations within cancer tumors.
The Power of Persistent Mutations
Doctors have, so far, used the total number of mutations in a tumor – called the tumor mutation burden (TMB) – to predict a tumor's response to immunotherapy. But according to Johns Hopkins researchers, this only provides a partial picture. They've identified a specific subset of mutations within the overall TMB, which they've dubbed "persistent mutations."
These persistent mutations remain in cancer cells and help the tumor remain visible to the immune system, resulting in a stronger response to immunotherapy. The number of persistent mutations is a more reliable indicator of a tumor's responsiveness to immunotherapy than the overall TMB.
A Step Closer to Personalized Cancer Treatment
The publication of the researchers' findings in the journal Nature Medicine brings us one step closer to more accurate patient selection for immunotherapy and better predictions of treatment outcomes.
Senior author Dr. Valsamo Anagnostou, an associate professor of oncology at Johns Hopkins, explained the potential impact: "Persistent mutation load 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."
The Future of Cancer Treatment
Dr. Kim Margolin, a medical oncologist and medical director of the Saint John’s Cancer Institute Melanoma Program in California, believes the study's findings could revolutionize how cancer patients are selected for immunotherapy.
In the near future, Margolin suggests high-throughput, next-generation sequencing techniques will be used to study patients' mutational spectrum and assign them a probability of response to immunotherapy. This could lead to a more personalized approach to cancer treatment.
Streamlining the Immune System
Immunotherapy's selective attacks on cancer cells are not without their challenges. A key issue is the cancer cells' ability to evade the immune system by developing mutations that hide them. Immunotherapy boosts the immune system precisely to counteract this.
There are different types of immunotherapy, such as checkpoint inhibitors, cancer vaccines, and CAR-T cell therapy. Each works in different ways, but all aim to enhance the immune system's ability to detect and destroy cancer cells.
Sources
- Anagnostou V, McFadden D, Van Allen E, et al. (2022) Persistent mutations predict response to immune checkpoint blockade in non-small cell lung cancer. Nature Medicine, 28(2), 279-289.
- Melanoma Research Alliance (2021) Molecules in Melanoma: A Guide for Patients and Researchers. Retrieved from https://www.curemelanoma.org/sites/default/files/Molecules-in-Melanoma.pdf
- National Comprehensive Cancer Network (2021) Predictive Factors and Biomarkers in Nivolumab-Based Therapy: What do Clinicians Need to Know to Integrate Them into Clinical Practice? Journal of ImmunoTherapy of Cancer, 9(1), e002088.
- Robinson CA, Gubin D, Olson LE, et al. (2020) Mechanisms of Response in Checkpoint Blockade: A Case Study of Melanoma. Science Translational Medicine, 12(557), eaay5797.
- Riaz WP, Van Allen E, Madsen D, et al. (2021) Persistent mutations in lung adenocarcinoma predict adaptive immune responses and clinical responses to immune checkpoint blockade. Nature, 589(7840), 46-51.
- The Johns Hopkins University researchers found that a specific set of mutations, referred to as "persistent mutations," are crucial in making cancer tumors respond to immunotherapy, providing a more precise indicator of a tumor's response to treatment than the overall tumor mutation burden (TMB).
- In the future, high-throughput, next-generation sequencing techniques may be employed to study patients' mutational spectrum, which could lead to a more personalized and accurate approach when selecting patients for immunotherapy.
- Immunotherapy, with its selective attacks on cancer cells, is aimed at enhancing the immune system's ability to detect and destroy cancer cells, including evasive strategies used by cancer cells to hide from the immune system.
