Predicting Immunotherapy Response: Scientists Discover Strategies to Foresee Results
Immunotherapy: Boosting the Body's Defense Against Cancer
In the ongoing battle against cancer, the latest weapon in the arsenal is immunotherapy - a treatment that utilizes the body's immune system to combat the disease. Even though immunotherapy offers new hope, not every person or every cancer responds to this treatment. Researchers at Johns Hopkins University have made a significant breakthrough by pinpointing a specific subset of mutations in cancer tumors that indicate how receptive it will be to immunotherapy.
This revolutionary discovery could revolutionize the way doctors select patients for immunotherapy and predict treatment outcomes. The research team's findings were recently published in the prestigious journal Nature Medicine.
What is Immunotherapy?
Immunotherapy is a treatment that leverages the body's immune system to identify and destroy cancer cells. Typically, cancer cells develop mutations that make them invisible to the immune system. Immunotherapy provides a boost to the body's immune system, enabling it to locate and eliminate these hidden cancer cells more effectively.
Immunotherapy comes in various forms, including:
- Immune checkpoint inhibitors (ICIs)
- Chimeric Antigen Receptor (CAR) T-cell therapy
- Monoclonal antibodies
- Cancer vaccines
- Adoptive cell transfer
- Cytokine therapy
Currently, some types of cancer like breast cancer, melanoma, leukemia, and non-small cell lung cancer can be treated with immunotherapy. Scientists are also investigating its potential for treating other cancers such as prostate cancer, brain cancer, and ovarian cancer.
Exploring Mutations
At present, doctors use the total number of mutations in a tumor - known as tumor mutational burden (TMB) - to gauge a tumor's potentialresponse to immunotherapy. Lead author of the study, Dr. Valsamo Anagnostou, an associate professor of oncology at Johns Hopkins, explained that TMB:
"...is the number of changes in the genetic material and particularly in the DNA sequence of cancer cells, known as mutations. A large number of mutations in cancer cells clearly distinguishes them from normal cells - in other words, renders them 'foreign' to the immune system and as such gives moreopportunities for the immune system to identify and attack the tumor."
However, the researchers noticed that not all persistent mutations contribute to a stronger immune response. To address this issue, they identified a specific subset of mutations they call "persistent mutations" that are more likely to remain present as cancer evolves. This ensures the cancer cells remain visible to the immune system, enhancing the body's response to immunotherapy.
According to Anagnostou, these persistent mutations:
"...may render the cancer cells continuouslyvisible to the immune system, eliciting an ongoing 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."
This study could help oncologists more accurately select patients for immunotherapy treatment and predict outcomes more accurately. Dr. Kim Margolin, a medical oncologist, added:
"Persistent mutations and mutation-associated neo-antigens that are efficiently presented by the patient's own complement of HLA class I and II molecules, 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 - mainly the immune checkpoint-blocking antibodies but also CAR T-cell therapy, vaccines, cytokine therapy, and even radiation therapy."
As the field of immunotherapy continues to grow and evolve, it is essential for doctors to stay up-to-date on the latest research and incorporates this knowledge into their treatment strategies for their patients. Persistent mutations could become crucial factors in determining a cancer patient's eligibility for immunotherapy as well as predicting their outcomes from the treatment. The future of cancer treatment could lie in harnessing the power of the immune system to eradicate this devastating disease.
Enrichment Data:Persistent mutations in cancer tumors that indicate a tumor's receptiveness to immunotherapy are primarily those that increase tumor mutational burden (TMB) or generate neoantigens recognizable by the immune system. Key mutational features include:
- Microsatellite instability-high (MSI-H) status, representing defective DNA mismatch repair mechanisms, leading to an abundance of neoantigens and a higher likelihood of immunotherapy responsiveness.
- High tumor mutational burden (TMB), characterized by a large number of somatic non-synonymous mutations, positively correlating with increased overall survival for patients treated with immunotherapy due to increased neoantigen production.
- Tumor-associated antigens (TAAs) produced from persistent somatic mutations. A high burden of TAAs, especially in combination with a favorable tumor immune microenvironment (non-exhausted immune context) and co-stimulatory signals, predict responsiveness to immunotherapy. These antigens serve as targets for T cell-mediated immune attack and are promising for vaccine development to improve immunotherapy outcomes.
Additional biomarkers complementing mutation indicators include PD-L1 expression levels and others, which also help predict immunotherapy efficacy, especially in non-small cell lung cancer (NSCLC) and other cancers. In summary, persistent mutations that create a high load of neoantigens—such as those found in MSI-H tumors, tumors with high TMB, and tumors rich in tumor-associated antigens—signal a higher likelihood of responsiveness to immunotherapy. These mutational markers serve as predictive biomarkers and guide personalized immunotherapy treatment strategies.
- Incorporating the latest scientific discoveries into medical practice is crucial for the effective selection of patients for immunotherapy treatment.
- A significant breakthrough in science has identified a specific subset of persistent mutations that render cancer cells continuously visible to the immune system, potentially enhancing the body's response to immunotherapy.
- Persistent mutations that generate a high load of neoantigens, such as those found in MSI-H tumors, tumors with high TMB, and tumors rich in tumor-associated antigens, may indicate a higher likelihood of responsiveness to immunotherapy, serving as valuable predictive biomarkers for personalized immunotherapy treatment strategies.
