Various immune cells help orchestrate a response against invading diseases. These cells make up a two-wave response system designed to quickly find foreign pathogens, target them, and generate cell memory to more efficiently recognize the infection the next time it enters the body. The first response includes innate immunity. This system surveys and recognizes pathogens quickly with little specificity. If the innate immune system cannot eliminate the disease, it will try to contain it and help build the adaptive immune response. The adaptive immune system comes after innate immune cells recognize the pathogen. Cells in this system are more specific with a primary goal to clear the body of all foreign invaders. Altogether, both innate and adaptive immune systems work in concert to elicit a strong and efficacious response to keep the body healthy and free from disease.
One type of immune cell that has gained interest within the research community includes natural killer cells (NK cells). These cells are part of the innate immune system and are one of the first responders to disease in the body. NK cells are a type of white blood cell responsible for targeting infections at early stages of progression. Specifically, they help contain and eliminate viruses and diseases, such as cancer. Scientists are beginning to use these cells in cancer treatment to direct the immune system toward hard-to-treat cancers. Currently, novel immunotherapies are being developed to use NK cells to effectively eliminate tumor burden.
A recent study in Cancer Cell, by Dr. Katayoun Rezvani and colleagues, demonstrated that NK cells can be engineered to effectively target glioblastoma cells. These cells were designed to express a protein known as interleukin-21 (IL21) and sustain long-term antitumor activity against a tumor in an extremely sensitive tissue. Rezvani is a Professor in the Department of Stem Cell Transplantation, and the Sally Cooper Murray Endowed Chair in Cancer Research at the University of Texas MD Anderson Cancer Center in Houston, Texas. Her research focuses on engineering immune cells to target hematological and solid malignancies. She specifically studies immune cells, such as NK cells and T cells, to better understand their function in the context of cancer and how to improve their antitumor activity.
Authors in the article describe new evidence that NK cells that secrete IL21 have significant antitumor activity against glioblastoma tumors in the brain. For the first time Rezvani and her team uncover a mechanism that promotes immunological memory in NK cells. Unfortunately, patients with glioblastoma have limited therapeutic options due to the location of the tumor and aggressiveness of the disease.
To overcome these obstacles, researchers have engineered NK cells to secrete IL21, which boost their antitumor immunity. When testing this treatment in animal models, they found the therapy increased specificity with few adverse effects. When investigating further, they identified intracellular proteins that regulate the activity of these cells. More experiments demonstrated that if the intracellular protein, known as CCAAT/Enhancer-Binding Protein D (CEBPD), was deleted, the antitumor activity of the NK cells lost its potency. These discoveries have major implications on future cancer immunotherapies and provides a fundamental understanding of how NK cells function. While this work needs to be validated in clinical trials, it offers a more effective option for glioblastoma patients.