LAT1 activates events that cause T cells to die from lack of tryptophan and toxic effects of kynurenines.
A group of scientists say that they found a biochemical cycle that suppresses the immune response thereby allowing cancer cells to multiply unabated. The research reportedly shows how the biomolecules responsible for healthy T cells are squashed permitting the invading cancer to spread.
“We used a technique called fluorescence resonance energy transfer, or FRET, to monitor the levels of tryptophan, one of the essential amino acids human cells need for viability,” explains lead author, Thijs Kaper at Carnegie Institution’s department of plant biology. “Tryptophan is essential for normal growth and development in children and nitrogen balance in adults. T cells also depend on it for their immune response after invading cells have been recognized.”
The researchers looked at the chemical transformations that tryptophan undergoes as it is processed in human cancer cells. When the amino acid is broken down in the cancer cells, an enzyme called IDO forms molecules called kynurenines. This reduces the concentration of tryptophan in the local tissues and starves T cells of tryptophan.
The study showed that a transporter protein known as LAT1 present in certain types of cancer cells exchanges tryptophan from the outside of the cell with kynurenine inside the cell, resulting in an excess of kynurenine in the body fluids, which is toxic to T cells.
“It’s double trouble for T cells,” comments Wolf Frommer of Carnegie Institution’s department of plant biology. “Not only do they starve from lack of tryptophan in their surroundings, but it is replaced by the toxic kynurenines, which wipes T cells out.”
The study was conducted by investigators the University Hospital of Heidelberg and Stanford University led by investigators at Carnegie Institution. It will be published in the September 25 issue of PLoS Biology.