Immunotherapy Outcomes Prediction: Scientists Discover Methods for Anticipating Responses
The Latest on Immunotherapy Against Cancer:
In the ongoing battle against cancer, immunotherapy has emerged as a promising new frontier.
Not all patients and cancers will respond to this groundbreaking treatment. Researchers from Johns Hopkins University are aiming to elucidate what factors contribute to a successful immunotherapy treatment outcome.
Their breakthrough discovery revolves around a specific subset of mutations present within a cancer tumor — a discovery they termed "persistent mutations." These persistent mutations make the cancer tumor visible to the body's immune system, improves the body's ability to find and destroy cancer cells, and potentially enhances the effectiveness of immunotherapy.
By incorporating persistent mutations into the equation, doctors might more accurately select patients for immunotherapy and predict the treatment's success more accurately. This exciting revelation has been published in the prestigious journal, Nature Medicine.
What is Immunotherapy?
Immunotherapy is a cancer treatment strategy that harnesses the power of the body's immune system to fight the disease. Typically, cancer cells develop mutations that allow them to evade detection by the immune system. Immunotherapy provides a vital boost to the immune system, empowering it to locate and destroy cancer cells.
Several forms of immunotherapy exist, including:
- Checkpoint inhibitors
- Adoptive cell therapies
- Cytokine therapies
- Oncolytic viruses
- Immunotoxins
The Power of Persistent Mutations
Traditionally, doctors have relied on the total number of mutations in a tumor — known as the Tumor Mutation Burden (TMB) — to predict how well a tumor will respond to immunotherapy. Dr. Valsamo Anagnostou, a senior author of the study and an associate professor of oncology at Johns Hopkins, explained:
"A large number of mutations in cancer cells clearly distinguishes them from normal cells, making them 'foreign' to the immune system. This is clinically translated into longer clinical outcomes with immunotherapy for some tumors that harbor a high tumor mutation burden."
However, Anagnostou and her team found that not all mutations in a tumor contribute equally to immunotherapy success. Specifically, they discovered persistent mutations that continue to exist within a tumor as it evolves, making the tumor more visible to the immune system and a better candidate for immunotherapy.
"Persistent mutations render the cancer cells continuously visible to the immune system, eliciting a stronger response," Anagnostou explained. "This response is augmented under the influence of immune checkpoint blockade, allowing the immune system to eliminate cancer cells harboring these persistent mutations over time, resulting in sustained immunologic tumor control and long survival."
Implications for the Future
The research published in Nature Medicine could dramatically alter the way oncologists approach immunotherapy for their patients. Dr. Kim Margolin, a medical oncologist and medical director of the Saint John's Cancer Institute Melanoma Program, believes that this study "demonstrates that a highly-respected collaborative group has gone beyond the simple concept of tumor mutation burden and defined persistent mutations, loss of mutation-containing sequences, and neo-antigens in a new light."
While much work still needs to be done, the discoveries made by Anagnostou and her team hint at a future where immunotherapy will be more personalized and effective against an even wider range of cancers.
Insights: The presence of persistent mutations in cancer tumors can indicate a better response to immunotherapy, particularly those that lead to a high tumor mutation burden (TMB) and the presence of specific neoantigens. Key mutations may include STK11, PD-L1, MET, and TP53. Tumor heterogeneity and genetic ancestry can also impact the prediction of immunotherapy response.
- The discovery of persistent mutations in a cancer tumor, as reported by researchers from Johns Hopkins University, may potentially enhance the effectiveness of immunotherapy.
- By focusing on the persistent mutations in a cancer tumor instead of the total number of mutations, doctors may be able to more accurately select appropriate patients for immunotherapy and predict the treatment's success more accurately.
- The study published in Nature Medicine suggests a future where immunotherapy will be more personalized, taking into account the presence of persistent mutations in individual cancer tumors, leading to a more effective treatment against a wider range of cancers.
