It was also found that after beta-glucan therapy the innate immune system generated a sort of memory which was held inside the bone marrow.
Immunotherapy is one of the many treatments for cancer. This therapy either stimulates the body’s own immune system to fight cancerous cells or involves the administration of substances made in the lab that can improve the immune system function to fight cancer cells.
Experts believe that immunotherapy affects the adaptive immune system — the immunity we acquire after being exposed to an antigen/threat.
Now, a group of researchers at the University of Pennsylvania say that the innate immune system may also have a role in the success of immunotherapy and specific cells in the immune system can be primed to target tumour cells.
The findings of their study are published in the peer-reviewed journal Cell.
The interplay between cancer cells and immune system
Our immune system has a complex reaction to tumours. Immune system cells infiltrate solid tumours and play an important role in tumour progression. The microenvironment in tumour cells reprogrammes the immune cells that infiltrate it so the latter start to facilitate tumour growth. Cancer also induces changes in the production of certain immune system cells including neutrophils and monocytes, which then acquire a specific structure that promotes tumours.
However, certain neutrophils that infiltrate tumours also turn cytotoxic and fight tumours. The tumour supporting and destroying neutrophils have distinct phenotypes (structure) and they can be differentiated by different cytokines and chemokine production patterns.
Together, all these immune system changes play an important role in the progression of cancer.
The latest study is based on previous evidence where researchers found that beta-glucan, a fungal compound, can stimulate the immune system to make more of certain cells (like neutrophils) and that this therapy can lead to better results from chemotherapy in mice. It was also found that after beta-glucan therapy, the innate immune system generated a sort of memory which was held inside the bone marrow. The researchers had called this behaviour ‘trained immunity’.
The latest study
For the latest study, the researchers injected mice intraperitoneally (peritoneum is a thin layer that covers the abdominal organs) with beta-glucan or a control solution first and then with melanoma cells (a type of cancer cells) after a week. They noted that mice who received beta-glucan showed less tumour progression even two weeks after injecting them with tumour cells than the mice in the control group.
The test group mice had trained immunity and it was not due to the adaptive immune system. However, there was no difference in the number of tumour infiltrating cells in the test and control group mice. Instead, more tumour-destroying neutrophils were present in the test group.
To confirm the findings, the researchers took neutrophils from the beta-glucan treated mice and injected them along with melanoma cells into a new set of mice. Tumour growth was suppressed in the new mice too. For another level of confirmation, the research team took another set of mice, destroyed their bone marrow and then transplanted the bone marrow of the beta-glucan treated mice in them. A control group was prepared. They received bone marrow from the control group in the first experiment after their own bone marrow was destroyed.
Both the groups were injected with melanoma cells. The mice that received bone marrow from beta-glucan treated mice fared better. The study indicated that this reaction was due to the memory of the immune system that is stored inside the bone marrow.
Further investigations revealed that genetic changes were occurring in the beta-glucan treated mice, causing them to make more anti-tumour neutrophils.
This is a breakthrough concept that can be therapeutically exploited for cancer immunotherapy in humans,” Dr George Hajishengallis, coauthor of the study, said in a news release by the University of Pennsylvania.
For more information, read our article on Immune system and immunity.
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