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Researchers are investigating how to make immunotherapy more effective in fighting cancer. SAUL LOEB/AFP via Getty Images
  • Immunotherapy is one of the newest treatment options against cancer.
  • Currently, not all people and all cancers can be treated by immunotherapy.
  • Researchers from Johns Hopkins have identified a specific subset of cancer tumor mutations that hint at how receptive a tumor will be to immunotherapy.

Every year, scientists develop new treatment options to fight cancer. One of the newest options is immunotherapy.

However, immunotherapy does not work for every person or every type of cancer. Researchers continue to look for answers as to what might cause immunotherapy to stop working.

Now, researchers from Johns Hopkins University in Maryland say they have found a specific subset of mutations in a cancer tumor that hints at how receptive it will be to immunotherapy.

Researchers believe their findings will help doctors more accurately select people for immunotherapy as well as better predict outcomes from the treatment.

Their study was recently published in the journal Nature Medicine.

Immunotherapy is a cancer treatment using the body’s immune system to fight the disease.

Usually, cancer cells develop mutations. These mutations allow the cancer cells to stay hidden from the body’s immune system.

Immunotherapy provides a boost to the body’s immune system, making it easier for it to find and destroy cancer cells.

There are a few different types of immunotherapy, including:

Immunotherapy is currently a treatment option for breast cancer, melanoma, leukemia, and non-small cell lung cancer.

Researchers are currently looking at using immunotherapy as a treatment for other types of cancer, including prostate cancer, brain cancer, and ovarian cancer.

According to the study’s researchers, doctors currently use the total number of mutations in a tumor — called the tumor mutation burden (TMB) — to try to figure out 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,” said Dr. Valsamo Anagnostou, a senior author of the study as well as an associate professor of oncology at Johns Hopkins, director of the thoracic oncology biorepository and co-leader of the Johns Hopkins Molecular Tumor Board and the Lung Cancer Precision Medicine Center of Excellence.

“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 more opportunities for the immune system to identify and attack the tumor,” Anagnostou told Medical News Today. “This is clinically translated into longer clinical outcomes with immunotherapy for some tumors that harbor a high tumor mutation burden.”

In this study, Anagnostou and her team identified a specific subset of mutations within the overall TMB — which they called “persistent mutations” — that are less likely to go away as cancer evolves.

This then allows the cancer tumor to remain visible to the body’s immune system, allowing a better response to immunotherapy.

“Persistent mutations are always there in cancer cells and these mutations may render the cancer cells continuously visible to the immune system eliciting an anti-tumor immune response,” Anagnostou said. “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. The number of persistent mutations more optimally identifies tumors that are more likely to respond to immune checkpoint blockade compared to the overall tumor mutation burden.”

“Persistent mutation load 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 checkpoint blockade,” she added.

Medical News Today also spoke with 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, about the study.

“It was refreshing to see this incredible article demonstrating that a highly-respective collaborative group has gone way beyond the simple concept of tumor mutation burden, PD-L1 expression, and tumor-infiltrating lymphocytes to define persistent mutations, loss of mutation-containing sequences, and mutation-associated neo-antigens in a new light,” she said.

“Persistent mutations and mutation-associated neo-antigens that are efficiently presented by the patient’s own complement of class I — and probably class II — MHC molecules and recognized by the patient’s own complement of T cell receptors 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 cytokines, bispecific immunomodulators, vaccines, Toll receptor agonists, growth factors and even radiation therapy,” Margolin added.

When asked how these findings may impact how cancer patients are selected for immunotherapy in the future, Margolin said it is likely that 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.

“And thus to categorize patients by their likelihood of response to immunotherapy — for advanced cancer — or their likelihood of benefit from adjuvant immunotherapy — patients who are apparently disease-free after definitive surgery,” she explained. “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 metastasis, where the elements of the immune tumor environment are critical elements.”