Predicting Immunotherapy Responses: Scientists Discover Methods for Anticipating Treatment Reactions
Every year, the fight against cancer continues to evolve, with immunotherapy being one of the latest treatment options. However, not all people and cancers respond favorably to this novel approach. In a groundbreaking study, researchers from Johns Hopkins University have identified a specific subset of mutations in a cancer tumor that could indicate a tumor's receptiveness to immunotherapy.
Researchers believe their findings will help doctors more accurately select patients for immunotherapy and better predict treatment outcomes. Published in the prestigious journal Nature Medicine, the study provides valuable insights into the intricate relationship between cancer mutations and immunotherapy efficacy.
Immunotherapy is a treatment strategy that harnesses the body's immune system to fight disease. Usually, cancer cells develop mutations that allow them to evade the immune system. Immunotherapy gives the immune system a boost, making it easier to find and eliminate cancer cells. There are several types of immunotherapy, including checkpoint inhibitors, CAR-T cell therapy, and vaccines, all designed to enhance the body's natural defense mechanisms.
Currently, immunotherapy is an effective treatment option for various cancers, such as breast cancer, melanoma, leukemia, and non-small cell lung cancer. Researchers are also exploring the use of immunotherapy for other types of cancer, including prostate, brain, and ovarian cancer.
For this study, the team led by Dr. Valsamo Anagnostou examined tumor mutation burden (TMB)—the total number of changes in a tumor's genetic material—to determine how well a tumor would respond to immunotherapy. They found a subset of mutations within the overall TMB, which they referred to as "persistent mutations." These mutations remain stable as cancer evolves, allowing the cancer tumor to stay visible to the immune system. As a result, cancer cells are more vulnerable to immunotherapy, leading to better treatment outcomes.
The researchers believe their findings will help clinicians better predict which patients are likely to respond to immune checkpoint blockade, a type of immunotherapy, and ultimately, improve treatment options for cancer patients.
In an interview with Medical News Today, Dr. Kim Margolin, a medical oncologist, commended the study for delving deeper into the concept of tumor mutation burden. She noted that persistent mutations, along with other factors such as specific CD8+ T cell responses and favorable tumor microenvironments, are critical to an effective anticancer immune response stimulated by immunotherapeutic agents.
Researchers are optimistic that this study will pave the way for the development of more personalized and efficient immunotherapy treatments for cancer patients in the near future. Further studies are expected to uncover more specific molecular alterations that can help improve immunotherapy outcomes.
Enrichment Data: The study has highlighted recurrent frameshift insertions and deletions (indels) as persistent mutations that generate novel open reading frame (ORF) peptides, termed frameshift neoantigens, which are highly immunogenic and can activate specific CD8+ T cell responses. These frameshift mutations are particularly important in cancers with microsatellite instability-high (MSI-H) and mismatch repair deficiency (dMMR). Specific frameshift mutations in genes such as SETD1B and RNF43 have been identified as producing immunogenic peptides that stimulate antitumor immunity. These shared frameshift neoantigens derived from recurrent mutations offer promising targets for developing precision immunotherapies with potential applicability across multiple cancer patients.
- Researchers found that a specific subset of mutations, referred to as "persistent mutations," could indicate a tumor's receptiveness to immunotherapy, which could help doctors more accurately select patients for this treatment and better predict treatment outcomes.
- The study revealed that recurrent frameshift insertions and deletions (indels) function as persistent mutations, generating novel open reading frame (ORF) peptides, or frameshift neoantigens, which are highly immunogenic and can activate specific CD8+ T cell responses.
- Specific frameshift mutations in genes like SETD1B and RNF43 have been identified as producing immunogenic peptides that stimulate antitumor immunity, offering promising targets for developing precision immunotherapies with potential applicability across multiple cancer patients.
