How Cancer “Changes Spots” to Evade Immunotherapy

How Cancer “Changes Spots” to Evade Immunotherapy

immunotherapy

New immunotherapy treatments have been successful at treating many cancer patients. But one of the main issues with the method is that it’s very hard to predict which patients will respond and which patients won’t. An entire sect of immunotherapy research is dedicated to figuring out ways to better predict patient response and improve the overall efficacy of the treatments. One study discovered that cancers actually find ways to evade immunotherapy treatments by “changing their spots” and hiding from the immune system.

The study, published in the Journal for Immunotherapy of Cancer, was led by researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust. The team grew miniature tumors in their labs to run tests on samples from patients with bowel cancer. By studying the molecular changes taking place within the mini tumors, they were able to determine which tumors were likely to respond to immunotherapy treatments.

In particular, the team was looking to find ways to increase the efficacy of promising new immunotherapy drug called cibisatamab. Cibisatamab is designed to act as a “matchmaker” between cancer cells and the immune system. The drug has shown promising results in its early trials, but many cancers were not responding to the treatment, so the researchers sought to find different ways they could make it effective for more patients.

immunotherapy

The study involved taking biopsies from eight patients with bowel cancer and using a new technique to grow “mini” tumor models in the lab. The results showed that three groups of cells: cells with high levels of carcinoembryonic antigen (CEA), cells with low levels of CEA, and cells with a mix of both high and low. Using cibisatamab to treat the tumors resulted in a decrease of growth by 96% in tumors with high CEA levels, but only 20% for low CEA levels, and 53% in tumors with mixed CEA levels.

immunotherapy

The team then used special equipment to separate the individual cells with high or low CRA and allowed them to settle for a month to create new tumors. They discovered that the CEA levels changed in the newly-grown tumors, which suggests that cells can modify themselves rapidly to enter a new state. This could be how cancerous cells hide from immunotherapy.

The good news is that the active genes in the mini tumors showed that cells with low CEA levels on the surface had more activity in the WNT pathways, which are being targeted by a few new drugs in development.

The team found that treating the mini bowel cancer tumors with drugs that target those pathways, such as tankyrase inhibitors and porcupine inhibitors, raised the CEA levels and made them more vulnerable to immunotherapy’s attack.

Dr. Marco Gerlinger, Team Leader in Translational Oncogenomics at The Institute of Cancer Research in London, believes that the results of this study  “could in future help immunotherapies work in more patients by making cancer cells more visible to immune cells.”

 

immunotherapy

While immunotherapy has provided oncologists and cancer patients with new, innovative ways to treat disease, it still does not work for every patient. As Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said, what makes immunotherapy so successful is likely also what makes it more difficult. It’s not a standard treatment. It’s individualized to fit the needs of each patient. “As we move away from one-size-fits-all therapy for cancer,” he said, “it’s so important that we are able to identify which patients are most likely to respond to a drug, and do everything we can to avoid resistance to treatment for as long as possible.”

The ability to use mini lab-grown tumors offers an innovative way to test treatments before going to clinical trials. A small biopsy can create a tumor model that accurately portrays a cancer patient’s cells. Studies like this one could be the key to improving the efficacy of immunotherapy treatments so that they are successful in a wider range of patients.

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