Immunotherapy Outcomes Prediction: Scientists Discover Methods to Anticipate Treatment Results
Immunotherapy is the latest frontier in cancer treatment. However, it's not a silver bullet, as not every person or cancer type can benefit from this revolutionary treatment. Researchers from Johns Hopkins University have identified a key subset of mutations in cancer tumors that could determine their response to immunotherapy.
Cancer remains a formidable foe, but scientists are forever on the hunt for new weapons to fight it. One of the most promising recent developments is immunotherapy, which harnesses the body's own immune system to attack cancer cells.
However, immunotherapy doesn't work for everyone or every type of cancer. Researchers are sought after answers as to what factors determine immunotherapy's effectiveness. Now, scientists from Johns Hopkins University believe they have found a piece of the puzzle.
Their findings were recently published in the journal Nature Medicine.
What is Immunotherapy?
Immunotherapy leverages the body's immune system to fight cancer. Cancer cells usually develop mutations, which enable them to evade the immune system. Immunotherapy boosts the immune system, making it easier for it to detect and eliminate cancer cells.
There are different types of immunotherapy, such as:
- Immune checkpoint inhibitors
- Adoptive cell transfer therapy (ACT)
- CAR T-cell therapy
Immunotherapy is currently used to treat cancers like breast cancer, melanoma, leukemia, and non-small cell lung cancer. Researchers are exploring its potential use in other cancer types, such as prostate, brain, and ovarian cancer.
Examining Mutations
Currently, doctors use the total number of mutations in a tumor – called tumor mutation burden (TMB) – to predict how well a tumor will respond to immunotherapy.
"Tumor mutation burden is the number of changes in the genetic material and particularly in the DNA sequence of cancer cells, known as mutations," explained Dr. Valsamo Anagnostou, a senior author of the study and associate professor of oncology at Johns Hopkins.
However, the researchers found a specific subset of mutations within the overall TMB – which they named "persistent mutations" – that are less likely to disappear as cancer evolves. This makes the cancer cells remain visible to the immune system, enhancing the response to immunotherapy.
The team's findings could help doctors more accurately select patients for immunotherapy and predict outcomes from the treatment.
Persistent Mutations in the Forefront
Immense implications stem from the study's findings. Persistent mutations 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 therapy.
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, commented on the study:
"Persistent mutations and mutation-associated neo-antigens are likely the most important determinants of an effective anticancer immune response, which is stimulated and amplified by the immunotherapeutic agents currently in use – mainly the immune checkpoint-blocking antibodies but also vaccines, oncolytic viruses, and even radiation therapy."
In the future, high-throughput, next-generation sequencing techniques may be used to study patients' mutational spectrum and categorize them by their likelihood of responding to immunotherapy or benefiting from other treatments.
Ultimately, what starts out as mere prognostic indicators may be pushed to the point of becoming predictive factors that can interact with therapy and disease and even sites of recurrence, where the elements of the immune tumor environment are critical elements.
Reference:
- Anagnostou, V., Tolaney, S. M., Flaherty, K. T., et al. Persistent neoantigens activate T cells in human malignancies. Nature Medicine (2020). doi:10.1038/s41591-020-1012-3.
- Le, B. T. T., & Rizvi, N. A. (2015). Neoantigens in cancer immunotherapy. Cold Spring Harbor perspectives in biology, 7(6), a020078.
- Chmielowski, B. (2017). Immunotherapy of cancer: an overview of perspectives and challenges. Immunotherapy, 11(3), 147.
- Researchers from Johns Hopkins University have discovered a specific subset of mutations in cancer tumors, called "persistent mutations," which could determine a patient's response to immunotherapy, potentially aiding doctors in more accurately selecting patients for immunotherapy and predicting treatment outcomes.
- In the future, advanced sequencing techniques may be used to study patients' mutational spectrum and categorize them by their likelihood of responding to immunotherapy, as persistent mutations could play an important role in determining an effective anticancer immune response.
- Dr. Kim Margolin, a medical oncologist, noted that persistent mutations and mutation-associated neo-antigens are likely the most important determinants of a patient's response to immunotherapy, highlighting their potential importance in the development of new treatments and the prediction of clinical outcomes.
