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Activate the immune system to attack cancer



Activate the immune system to attack cancer

The so-called innate immune system training can stimulate a stronger immune response against threats such as cancer. An international team led by Penn Dental Medicine researchers studied the mechanism by which training works in the body.Image source: Hajishengallis Laboratory

Immunotherapies such as checkpoint inhibitor drugs have been very different in treating cancer. Most clinicians and scientists understand that these drugs work on the adaptive immune system, T cells and B cells that respond to specific threats in the body.

New research conducted by an international team led by George Hajishengallis of the University of Pennsylvania School of Dentistry has shown that the innate immune system may play an important role in the success of immunotherapy, but it has been overlooked. The system̵

7;s response to human intruders is more extensive.

Their work is published in a magazine cellResearchers have found that “training” the innate immune system with β-glucan (a compound derived from fungi) can stimulate the production of innate immune cells (especially neutrophils), which are used to prevent Or attack tumors in animal models.

“The focus of immunotherapy is on adaptive immunity, just as checkpoint inhibitors inhibit the interaction between cancer cells and T cells,” said Hajishengallis, co-senior author of this work. “Innate immune cells or myeloid cells are not considered so important. However, our research shows that myeloid cells play a key role in regulating tumor behavior.”

The current research is based on cell Cooperated by Hajishengallis and a group of multi-institutional collaborators, research has shown that well-trained immunity caused by exposure to the fungus-derived compound β-glucan can improve the immune recovery of mouse models after chemotherapy.

In previous studies, the researchers also showed that the “memory” of the innate immune system is stored in the bone marrow, that is, in hematopoietic stem cells, which are the precursors of granulocytes, such as neutrophils, monocytes and Macrophages.

The team next wants to understand the details of the memory encoding mechanism. Hajishengallis said: “The fact that β-glucan can help you fight tumors does not necessarily mean that it is achieved through well-trained immunity.”

To confirm this connection, the researchers isolated neutrophils from innate immune-trained mice exposed to β-glucan, and transferred them and cells that grew into melanoma tumors to those that did not receive β-glucan. Sugar in mice. In animals that obtained cells from trained mice, tumor growth was significantly inhibited.

To further support this link between myeloid precursors and the quality of protection of trained immunity, scientists performed bone marrow transplants, which effectively transferred bone marrow cells from “trained” mice to mice that were not irradiated. Eliminate their own bone marrow.

When challenged later, the trained mice received bone marrow treatment much better than the untrained mice received bone marrow treatment. Triantafyllos Chavakis of the Dresden University of Technology, a long-term collaborator of Hajishengallis and co-senior author of the study, said: “This is an inherent immune memory at work.”

This experiment relies on the memory of bone marrow precursors of neutrophils from trained donor mice, which are transferred to recipient mice by transplantation, thereby producing neutrophils with killing ability.

The researchers found that, compared with untrained neutrophils, trained neutrophils produce higher levels of reactive oxygen species or reactive oxygen species, which may be the result of anti-tumor activity. ROS may cause harm in some cases, but it may be beneficial in cancer because it can kill tumor cells.

Researchers carefully observed the myeloid precursors in the bone marrow of trained animals and found that the gene expression has undergone major changes, which bias the cells to produce neutrophils, especially the types associated with anti-tumor activity. This classification is called Neutrophil type I (TAN1) associated with tumors.

Further studies have shown that these changes caused by innate immune training cause epigenetic changes in bone marrow precursor cells, which make certain genes easier to be transcribed, and also point out that type I interferon signaling pathways may be innate immune Conditioner. training. Indeed, mice lacking type I interferon receptors cannot produce well-trained neutrophils.

Beta-glucan is already in clinical trials for cancer immunotherapy, but the researchers say this discovery indicates a new mechanism of action for new treatments.

Hajishengallis said: “This is a breakthrough concept that can be used in human cancer immunotherapy, especially by transferring neutrophils from donors trained in β-glucan to cancer patients who will become recipients. Come in.”


By changing the bone marrow, training can prepare the innate immune system for future challenges


More information:
Lydia Kalafati et al. Innate immune training for granulocyte production can promote anti-tumor activity. cell. Volume 183, Issue 3, P771-785.E12, October 29, 2020 DOI: 10.1016 / j.cell.2020.09.058

Journal information:
cell

Provided by the University of Pennsylvania

Citation: Starting the immune system to attack cancer (October 29, 2020) Retrieved from https://medicalxpress.com/news/2020-10-priming-immune-cancer.html on October 30, 2020

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