Hypermutated Brain Tumors Can Still Evade Immunotherapy

Immunotherapy is becoming the standard of care for many cancers, utilizing the body’s own immune system to fight cancer cells. Checkpoint inhibitors, one form of immunotherapy, allow the immune system to find and fight cancerous cells. Cancers of the bladder, breast, cervix, colon, esophagus, head, neck, kidney, blood, liver, lung, prostate and skin can all be treated with various forms of immunotherapy. One type of cancer that has proven very difficult to treat with immunotherapy is brain cancer, especially gliomas (glioblastoma multiforme or GBM). As cancers mutate, they often can become easier for the immune system to recognize with immunotherapy, but this is not the case for gliomas.

A glioma analysis published in the journal Nature looked at 10,200 cases of gliomas and found that immunotherapy is largely ineffective at treating this form of brain cancer. Typically, as a cancer mutates, it loses some resistance to the human immune system, which allows checkpoint inhibitor treatments to expose the cancer. However, even after several mutations, glioma cells still evaded the immune system after checkpoint inhibitor immunotherapy. Researchers believe that several immunosuppressive activities in the brain may help shelter gliomas from the immune system. Further research will be needed to discover how to expose gliomas to more cytotoxic lymphocytes, which are key cells in fighting disease.

This study also showed that the standard chemotherapy treatment for gliomas, temozolomide, becomes less effective if the glioma mutates, making the cancer harder to treat. Temozolomide is largely ineffective on hypermutated gliomas, as is immunotherapy. Ultimately, this analysis explains why gliomas, and especially glioblastomas, are known for their resistance to traditional cancer therapies and provides further insight into the treatment of gliomas with standard and new cancer therapies, paving the way for additional research.

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