New approaches for treating cancer are emerging all the time, and one exciting field is finding ways to boost anti-cancer mechanisms already present in the immune system. Now researchers in the US have discovered a new way to dramatically boost the capacity of certain immune cells to fight cancer. They write about their findings in the 8 December online issue of the Journal of Investigative Dermatology.
Dr Charles J. Dimitroff and colleagues in the Dimitroff Lab at Brigham and Women’s Hospital, a teaching affiliate of Harvard Medical School in Boston, Massachusetts, have discovered that lowering the biosynthesis of certain carbohydrates that adorn the cell surfaces of effector immune cells can dramatically boost their capacity to fight cancer.
Effector cells are a part of the immune system that kills pathogens such as bacteria, viruses and tumor cells. One of their functions is to recognize their target.
Previous studies had already suggested that a protein called Galectin-1 (Gal-1) plays a major role in helping tumor cells evade destruction by the immune system by triggering cell-death or apoptosis in immune effector cells. They have also shown that more aggressive and developed tumors express more Gal-1.
These studies have raised interest in targeting this protein for both cancer diagnosis and treatment.
For their study, Dimitroff and colleagues tested the idea that Gal-1 helps cancer cells to evade antitumor immune cells, and that it does this by binding with N-acetyllactosamines, a family of carbohydrate molecules.
To do this they took lab mice with melonoma or lymphoma and treated them with peracetylated 4-fluoro-glucosamine (4-F-GlcNAc), a compound that inhibits the production of N-acetyllactosamine by cells.
They then monitored what happened to the mice’s tumors and immune system.
They found that 4-F-GlcNAc stopped Gal-1 from triggering cell death in immune system’s T cells and NK (natural killer) cells by decreasing the amount of N-acetyllactosamine carbohydrate molecules expressed on their surfaces.
The compound also helped the immune cells infiltrate the tumors, and promoted higher levels of tumor-specific immune cells.
The result, remarkably, was negligible tumor growth.
The authors conclude:
“Collectively, our data suggest that metabolic lowering of Gal-1-binding N-acetyllactosamines may attenuate tumor growth by boosting antitumor immune cell levels, representing a promising approach for cancer immunotherapy.”
Thus they hope their findings offer a new target for therapies that boost the immune system’s existing pathways for fighting cancer.
Grants from the National Cancer Institute and the National Center for Complementary and Alternative Medicine, of the National Institutes of Health, helped pay for the study.
Written by Catharine Paddock PhD