The fast-paced scientific discoveries over the last 30-years have advanced the field of medicine and improved millions of patient lives. Specifically, immunotherapy has revolutionized the way physicians treat patients with cancer. Although chemotherapy, surgery, and radiotherapy are all still used as standard-of-care therapy for a majority of cancer types, immunotherapy enhances some of these treatments. Physicians are now combining standard treatment with immunotherapy to elicit optimal response.
Immunotherapy is designed to redirect the immune system to the cancer. As a tumor develops and is established, the immune system becomes ignorant of the tumor mass due to proteins and molecules that it secretes. These various secreted factors polarize immune cells to ignore the rapidly growing tumor cells or promote its growth. Immunotherapy helps to eliminate those tumor-promoting cells and allow the immune system to recognize the fast-growing cancer.
Immunotherapy has shown promise in various cancers with limited efficacy in others, including gliomas or brain cancer. Gliomas are a group of brain cancers that stem from a brain cell known as a glial cell. There are several types of gliomas dichotomized by the type of glial cell involved and the aggressiveness of the cancer. Like many other brain tumors, gliomas can cause seizures, memory loss, vision problems, personality changes and others. Scientists have been working on understanding more about gliomas and why immunotherapy is ineffective.
A recent study in Nature, by Dr. Bradley Bernstein and others, demonstrated how various cell populations within gliomas influence immunity and that anti-swelling medication further limits immunotherapy. Bernstein is a physician-scientist and Chair of Cancer Biology at the Dana-Farber Cancer Institute, Harvard Medical School. His work focuses on brain tumors and the gene expression of different cell types that influence cancer progression.
Bernstein and his team analyzed immune cells from 85 patients with glioma. Through next generation sequencing and computational methods, researchers identified sets of gene expressions that coordinated with function of different cell populations. The gene sets help further identify suppressive cells that allow the tumor to grow. As a result, this better informs scientists how to generate optimal medications. Moreover, the different functions of cell populations improve our understanding of the glioma-immune cell interactive dynamic and how to modulate these groups for therapy.
The team identified four subtypes of immune cell populations with different functions. Two of the groups were inflammatory and expressed markers correlating with anti-tumor function. The other two populations had markers correlating with immune cell suppression and pro-tumor function. Further analysis revealed that the cells with pro-tumor functions were from patients treated with an anti-swelling medication known as dexamethasone. While it was previously believed that dexamethasone had minimal effect on immunotherapy, researchers now realize the detrimental impact it has on various immune cells. Anti-swelling medication is a common treatment for glioma. Since patients experience headaches and nausea, medications, including dexamethasone, are given to help reduce inflammation and offset these symptoms.
To confirm their findings, Bernstein and others used 3D models of cells from patient tumors and treated with dexamethasone. They found that the immune cells in the cluster of cells were suppressive and promoted tumor growth even after the drug was removed. The work done by Bernstein and others is groundbreaking since many treatment regimens prescribe dexamethasone. This discovery will change the way physicians treat their patients and informs scientists about how to enhance therapies based on cell-to-cell interactions in gliomas.
Study, Nature, Bradley Bernstein, Dana-Farber Cancer Institute, Harvard Medical School
