One way to treat cancer is through immunotherapy or boosting the body's defenses against cancer cells by targeting the adaptive immune system, which triggers B-cells and T-cells. New research suggests that the innate immune system also plays an important role in response to cancer.
A study led by the University of Pennsylvania was recently published in the journal Cell. International scientists developed a new method to train the innate immune system to prevent or attack tumors.
Innate immunity contains nonspecific defense mechanisms in the presence of antigens. The mechanisms include barriers such as the skin, chemicals in the blood, and cells that attack intruders.
The immune system also has adaptive immunity which triggers an antigen-specific response. The more complex system processes and analyzes the intruding antigen that triggers an army of immune cells. Adaptive immunity also stores memory cells to efficiently attack returning antigens.
Training the Innate Immune System
In the new study, the team focused on specific innate immune cells called neutrophils. Using mice models, the cells were trained or primed to attack tumors using a compound derived from a fungus called β-glucan in the form of the Bacillus Calmette-Guėrin vaccine.
The Bacillus Calmette-Guėrin vaccine was developed in the early 1900s to protect the immune system against tuberculosis and leprosy. The vaccine is typically administered in newborns and infants.
George Hajishengallis said the previously, myeloid cells (innate immune cells) were not considered important. Immunotherapies are typically focused on adaptive immunity such as interactions between T-cells and cancer cells. However, the team's research suggests the important role that myeloid cells play in regulating tumor behavior.
Training myeloid cells with β-glucan resulted in improved immune recovery after chemotherapy. The memory of the innate immune system is found in the bone marrow or hematopoietic stem cells. "The fact that β-glucan helps you fight tumors doesn't necessarily mean it was through trained immunity," explained Hajishengallis.
New Method of Immunotherapy
In the mice models, the neutrophils exposed to β-glucan from mice models were given to mice with cells that developed into melanoma tumors. Tumor growth was hindered when mice received trained cells.
The team also performed bone marrow transplants by transferring trained cells to untrained mice. Treatment was effective once again. Triantafyllos Chavakis from Technical University Dresden in Germany explained that it was "innate immune memory at work."
Antitumor activity from trained neutrophils most likely produced more reactive oxygen species (ROS) or signaling molecules that damage cells. However, ROS can also kill tumor cells.
The researchers also discovered that certain genes can regulate innate immune priming. For example, mice without type I (TAN1) neutrophils could not produce trained neutrophils.
"This is a breakthrough concept that can be therapeutically exploited for cancer immunotherapy in humans," Hajishengallis says, "specifically by transferring neutrophils from β-glucan-trained donors to cancer patients who would be recipients." Currently, β-glucan is undergoing clinical trials for cancer immunotherapy.
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