Dr. Tenzin Gayden- first author and member of an international research team shown at the Jabado Lab in Montreal (RI-Muhc)

New immunology discovery to fight cancer and more

The human body is a remarkably complex and yet efficient machine. Scientists are learning more and more about how the machine works and the tiniest parts can play a big role.

New discoveries have been taking place in the area of immunology and genetics and the role of tiny proteins.  The latest involves a protein called TIM-3. An international team of researchers has discovered the molecule’s important role in regulating the immune system. The discovery appears to lead towards a relatively rapid available treatment in a rare form of cancer-like disease. The discovery has wider implications as well.

Dr Nada Jabado (MD, PhD) clinician scientist at the Montreal Children’s Hospital  part of the McGill University Health Centre.

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The human immune system is an amazing defence mechanism and proteins are programmed to activate when needed, and limit its function (checkpoint) when not needed.

L:-R: Dr. Tenzin Gayden (first author) and Dr. Nada Jabado (lead author) (Ri-MUHC)

When a brother and sister in Montreal developed the same rare cancer-like disease, doctors suspected a genetic issue.

What the international team discovered was a genetically inherited mutation on a particular “checkpoint” protein, TIM-3 which is needed to put the “brakes” on the immune system.  What they found was because of the  alteration of TIM-3, the immune system was not being shut down, and the aggressive system was attacking the body causing the cancer-like condition.

The research has been published in the science journal, Nature Genetics, under the title, “Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome” (abstract HERE)

From left to right: Dr. Tenzin Gayden , Dr. Sharon Abish, Dr. Nada Jabado and Dr. David Mitchell (Research Institute of the MUHC, Glen site) joined forces and expertise to solve a medical mystery that originated at the Montreal Children’s Hospital, leading to an important international discovery. (RI-MUHC)

With this new knowledge that this specific genetic mutation is allowing an overactive immune system damaging the body, Dr Jabado says the conditions can be rectified with simple immune system suppressor medication which slows down the system the way a normal TIM-3 would.

Dr Jabado also says that with the knowledge of of the TIM-3 role, clinicians could also use it in the body’s own fight against cancers. The immune system normally won’t attack it’s own cells when properly controlled by the various proteins.

But, she says, they should be able to manipulate the protein in the opposite role by shutting it’s action down with “checkpoint inhibitors”. This would allow the immune system to be more aggressive and attack those body cells which have been altered by cancer.

Identifying the role of TIM-3 adds to the known list of checkpoint proteins that have been discovered and greatly advances the work in immunology and will give clinicians more knowledge in fighting cancers and similar diseases, possibly as well in dealing with HIV and Multiple Sclerosis |(MS).

The research was conducted by scientists and physicians from the Research Institute of the McGill University Health Centre (RI-MUHC) and the Montreal Children’s Hospital of the MUHC (MCH-MUHC), in collaboration with French teams from AP-HP, Inserm, Université Paris-Descartes and the Imagine Institute at the Necker-Enfants Malades hospital.

This work was supported a grant from the Fondation des étoiles, INSERM, CNRS, l’AP-HP, Université Paris-Descartes and Collège de France.

Dr Jabado would also like to thank colleagues in France and Australia for their collaboration, and the many volunteers who donated genetic materials to advance the research.

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