Immunotherapy Outcomes Prediction: Scientists Discover Strategies for Anticipating Treatment Results
Modern cancer treatments continue to evolve, and immunotherapy is one such development. This innovative method leverages the body's immune system to fight the disease.
However, not every individual or cancer type responds favorably to immunotherapy. Scientists have been on a quest to understand the factors that determine its success. Recently, researchers from Johns Hopkins University have shed some light on this topic.
In their study, published in Nature Medicine, these scientists identified a particular subset of mutations within cancer tumors, dubbed "persistent mutations." These mutations persist and allow the cancer to remain visible to the immune system, leading to a better response to immunotherapy.
Doctors currently consider the total number of mutations in a tumor, called the Tumor Mutation Burden (TMB), to gauge a cancer's receptiveness to immunotherapy. However, the new findings suggest that focusing on persistent mutations might offer a more accurate way to select individuals for immunotherapy and predict treatment outcomes.
"Persistent mutations are always there in cancer cells and these mutations may render the cancer cells continuously visible to the immune system, eliciting a stronger and more sustainable immune response," explained Dr. Valsamo Anagnostou, a senior author of the study and an associate professor of oncology at Johns Hopkins.
This groundbreaking research could revolutionize how oncologists choose patients for immunotherapy and predict treatment outcomes.
What is Immunotherapy?
Immunotherapy is a treatment approach that utilizes the body's immune system to combat disease. Normally, cancer cells develop mutations that help them evade the immune system. Immunotherapy offers a boost to the immune system, making it easier for it to detect and destroy cancer cells.
There are several types of immunotherapy, including immune checkpoint inhibitors, CAR T-cell therapy, and immune modulators.
The Future of Immunotherapy
The findings of Johns Hopkins researchers could potentially lead to more accurate patient selection for immunotherapy trials and improved outcome predictions. By focusing on persistent mutations, doctors could identify tumors that are more likely to respond to immune checkpoint blockade and deliver personalized treatment strategies.
"In the not-too-distant future, it will be possible to use high-throughput, next-generation sequencing techniques to study patients' mutational spectrum such as was done in this study," said Dr. Kim Margolin, a medical oncologist at Providence Saint John's Health Center in California.
The study Portends a promising future for cancer treatment, where personalized immunotherapy based on specific mutations could become the norm.
Enrichment Data
The Johns Hopkins research focuses on specific mutations in the proofreading domains of the POLE and POLD1 genes. These mutations impair the exonuclease activity responsible for DNA replication fidelity, leading to a high tumor mutational burden and increased tumor-infiltrating lymphocytes (TILs). TILs are associated with better responses to immune checkpoint inhibitors such as nivolumab.
In particular, pathogenic POLE mutations predict improved responses to PD-1 blockade immunotherapy in tumors that are otherwise mismatch repair proficient (pMMR). Tumors harboring pathogenic POLE mutations demonstrate higher clinical benefit rates from PD-(L)1 based immune checkpoint inhibitors, including significantly improved progression-free survival, overall survival, and duration of response compared to tumors without these mutations.
Thus, the presence of pathogenic POLE/POLD1 proofreading domain mutations is a key genomic biomarker identified by Johns Hopkins research for predicting a tumor’s receptiveness to immunotherapy.
[1] Data refers to research published in journal Nature Medicine, volume 26, number 7, 2020, 1241-1250.
- The body's immune system is utilized in immunotherapy, a modern cancer treatment approach, to fight the disease, even as cancer cells develop mutations to evade the immune system.
- A study by scientists from Johns Hopkins University, published in Nature Medicine, identified a subset of persistent mutations in cancer tumors, which could offer a more accurate way to choose individuals for immunotherapy and predict treatment outcomes.
- These persistent mutations, or "persistent mutations," keep the cancer visible to the immune system, leading to a stronger and more sustainable immune response.
- The total number of mutations in a tumor, called the Tumor Mutation Burden (TMB), is currently used to gauge a cancer's receptiveness to immunotherapy, but the new findings suggest that focusing on persistent mutations could yield more accurate results.
- In the future, personalized immunotherapy based on specific mutations could become the norm, revolutionizing how oncologists choose patients for immunotherapy trials and predict treatment outcomes.
- The Johns Hopkins research identifies pathogenic POLE/POLD1 proofreading domain mutations as a key genomic biomarker for predicting a tumor’s receptiveness to immunotherapy, especially for tumors with pathogenic POLE mutations demonstrating higher clinical benefit rates from PD-(L)1 based immune checkpoint inhibitors.
