A new study has identified novel mechanisms by which T cells could distinguish an emerging class of targets specifically increased on cancer cells.
The study was carried out by researchers from the University of Birmingham and the University of Virginia and published in Oncotarget. The study focuses on Phosphorylation– how the immune system recognizes protein targets that are modified by this process. It is known to be more commonly found in cancer cells.
Phosphorylation plays a key role in cell signaling pathways. It involves small phosphate groups being added by kinase enzymes onto amino acid groups within a protein. It is recognized as being key to control a wide range of cellular pathways, including those that regulate cell division. Such pathways become heavily dysregulated in cancer.
Previous research published by authors reveal that such phosphorylated protein fragments can be presented on the surface of cancer cells for immune recognition. The ways in which such small modifications affect T cell recognition have remained unclear.
The lead author of the study, Dr. Daniel Stones from the Cancer Immunology and Immunotherapy Centre at the University of Birmingham, explains that “the small modification- phosphorylation- is likely to have major effect on how T-cells recognize these cancers associated targets in two ways”.
1st– Phosphorylation induces major change in overall structure of these peptides. 2nd The critical receptor involved on the T cell – T cell receptor – is very sensitive at directly discriminating modified from non-modified peptides- even when the changes induced are quite small.
The findings emphasize the growing interest in targeting modified antigens in cancer. The study reports the idea that abnormal patterns of phosphorylation seen in cancer cells may translate into a distinctive cancer-specific signature that can be targeted by the immune system. There are number of ways about targeting such phosphorylated peptides therapeutically such as vaccination, cellular therapies and protein therapeutics.