A new study has identified novel mechanisms where T cells may be able to differentiate an emerging class of targets specifically increased on Cancer cells.
Researchers from the University of Virginia and Brimingham have published their study in Oncotarget, focuses on how immune system recognizes protein targets that are modified by phosphorylation- it is known to be commonly increased in cancer cells.
Phosphorylation- plays a key role in cell signaling pathways and involves small phosphate groups being added by kinase enzymes onto amino acid groups within a protein. It is recognized as being key to the control of a wide range of cellular pathways, including that regulate cell division, and these pathways become dysregulated in cancer.
Previous research suggests that phosphorylated protein fragments present on surface of cancer cells for immune recognition, however the ways in which such small modifications affect how T cells recognize them have remained unclear. The team’s result has thrown light on this issue.
As explained by one of the key authors, Dr. Daniel from the cancer immunology and immunotherapy center at the university of Brimingham, phosphorylation – is likely to have major effect on how T cells can recognize these cancer-associated targets in two ways.
Phosphorylation induces a major change in the overall structure of these peptides. Then, the critical receptor involved on the T cell – the T cell receptor – is very sensitive at directly discriminating modified from non-modified peptides- even when the changes are relatively small.
overall, the findings underline growing interest in targeting modified antigens in cancer. The abnormal patterns of phosphorylation observed in cancer cells may translate into a distinctive cancer-specific signature that can be targeted by the immune system. There might be several ways to target such phosphorylated peptides therapeutically including vaccination, cellular therapies and protein therapeutics.