A revolutionary study conducted by a team of scientists at the renowned Salk Institute has found that a certain type of immunotherapy is able to train the brain’s ‘invisible scalpel’ to work on an incurable type of brain cancer in mice.
Glioblastoma happens to be the most common form of brain tumor, as well as the most deadly. However, our brains actually come equipped with immune cells that have the ability to destroy them.
Glioblastoma is a particularly deadly brain tumor known for its highly aggressive nature and high fatality rate. On the other hand, the human brain is equipped with immune cells capable of preventing these tumors.
However, glioblastomas possess highly intricate mechanisms that allow them to evade one’s immune system. But thankfully, with immunotherapy – although not necessarily effective for all – many tumors can be treated, even cured, using this process by enabling the immune system to pierce through these evasive tactics and obliterate cancer.
Leading this pioneering research is Professor Susan Kaech, the director of the NOMIS Center for Immunobiology and Microbial Pathogenesis. Her team embarked on a mission to explore the potential immunotherapy in tackling glioblastomas. To achieve this, they conducted experiments involving an immunotherapy drug known as anti-CTLA-4 and two specialized immune cell types: CD4+ T cells and microglia.
Professor Susan Kaech, senior author of the paper published in the journal Immunity, said, “There are currently no effective treatments for glioblastoma—a diagnosis today is basically a death sentence.”
“We’re extremely excited to find an immunotherapy regimen that uses the mouse’s own immune cells to fight the brain cancer and leads to considerable shrinkage, and in some cases elimination, of the tumor,” she added.
Anti-CTLA-4 and CD4+ T cells have, until now, remained relatively overlooked and less favored in clinical research. This was primarily due to the early years of immunotherapy research, which identified more effective alternatives.
For example, another immunotherapy agent called PD-1 was deemed more effective in various cancer models but failed to yield results in glioblastoma cases. In contrast, anti-CTLA-4 showed remarkable promise in glioblastoma therapy. This drug functioned by inhibiting the production of CTLA-4 protein, which, when unblocked, hampers the activity of CD4+ T cells, critical components of the immune system’s response.
The researchers made a groundbreaking discovery during their experiments. They found that when CD4+ T cells were allowed to function without inhibition, they secreted a vital protein known as interferon-gamma. This protein plays a dual role in combating glioblastomas.
Firstly, it caused the tumor cells to emit “stress flags,” a phenomenon that signaled their vulnerability. At the same time, the released interferon-gamma acted as a beacon, altering microglia, specialized immune cells adapted for the brain’s unique environment. These microglia, primed and ready, began to engulf the stressed tumor cells.
Co-first author, Siva Karthik Varanasi, a postdoctoral researcher in Kaech’s lab said, “We were stunned by this novel codependency between microglia and CD4+ T cells. We are already excited about so many new biological questions and therapeutic solutions that could radically change treatment for deadly cancers like glioblastoma.”
Remarkably, this process set in motion a self-sustaining cycle of destruction. As microglia consumed stressed-out tumor cells, it triggered the release of even more interferon-gamma from the tumor, prompting further consumption. This feedback loop continued until the entire tumor was devoured, offering a glimmer of hope in the battle against glioblastoma.
The next phase of this cutting-edge research involves investigating whether this cancer-killing cycle exists in human glioblastoma cases. Researchers are eager to determine if this approach holds promise for human patients. Additionally, they plan to expand their study by examining various animal models with different subtypes of glioblastoma, aiming to enhance our understanding of the disease and identify the most effective treatments.
In essence, the Salk Institute’s recent findings open up a compelling avenue for the treatment of glioblastoma, one of the most formidable adversaries in the realm of cancer. Through the innovative use of immunotherapy, it appears that the “invisible scalpel” of the brain can be wielded against this relentless enemy, offering newfound hope to patients and researchers alike.
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