Researchers from the University of Michigan (MI, USA) have discovered in mice a new protein termed galectin-1, which may allow high-grade gliomas to go undetected by the host’s immune system. The work was published on 7 August 2014, and has impacted the way researchers think about glioma formation.
The serendipitous discovery was made when researchers attempted to overproduce the protein in preclinical animal models of the disease. Instead they found that when they blocked production of galectin-1 the tumors were eradicated. Eradication of the tumors occurred via natural killer cells, which were able to recognize the tumors and eliminate them.
Overproduction of galectin-1 was demonstrated to mask the tumors, preventing the immune system from triggering a secondary T-cell response. The prevention of a secondary response enables brain tumors to be masked for so long that the host’s immune system cannot recognize them until the tumor is already too large.
Lead scientist Pedro Lowensteinnstein (University of Michigan Department of Neurosurgery) discussed the potential clinical applications of the study for patients with gliomas and the implications for research of discovering galectin-1. “In this case, we found that overexpression of galectin-1 inhibits the innate immune system, and this allows the tumor to grow enough to evade any possible effective T-cell response,” he explains. “By the time it’s detected, the battle is already lost.”
The researchers are hopeful that elucidation of galectin-1 will present an opportunity for the development of future therapies that may be effective against gliomas in patients, especially considering that these tumors represent 80% of all malignant brain cancers.
Current therapy for glioma patients involves surgical removal of tumors. Unfortunately the tumors often grow with tiny tendrils that extend into brain tissue, which means that neurosurgeons are limited and can only remove the bulk of the tumor. The tiny tendrils are often undiscovered and continue to grow within the brain. The findings of the galectin-1 study could, in future, provide a method of treatment without the need of surgery.
While the implications of this study offer a potential method of controlling gliomas in the future, the researchers stressed the importance of further research. Particular importance was placed on the extensive work required to translate the work from mice to humans.
Source: Baker GJ, Chockley P, Yadav VN et al. Natural Killer Cells Eradicate Galectin-1 Deficient Glioma in the Absence of Adaptive Immunity. Cancer Res. doi: 10.1158/0008-5472.CAN-14-1203 (2014) [Epub ahead of print]; University of Michigan Health System press release