Researchers have identified pancreatic cancer-specific cryptic antigens that can be targeted by T cells for recognition. These cryptic antigens are generated from the noncoding genome in cancer and can be presented by human leukocyte antigen class I (HLA-I). However, the cancer specificity and immunogenicity of these noncanonical HLA-I-bound peptides (ncHLAp) are not fully understood.
In a study published in the journal Science Translational Medicine, a team of researchers used high-resolution mass spectrometry to identify ncHLAp in pancreatic cancer tissue samples. They found that these cryptic antigens were present in all of the tumor samples tested, but not in normal tissue samples.
Further analysis revealed that these ncHLAp were derived from noncoding regions of the genome and were not previously known to be presented by HLA-I. This suggests that the noncoding genome may play a larger role in cancer development and immune recognition than previously thought.
The researchers also found that these ncHLAp were highly specific to pancreatic cancer, as they were not present in other types of cancer or normal tissues. This is a promising finding as it suggests that these cryptic antigens could potentially be used as biomarkers for early detection of pancreatic cancer.
In addition, the team observed that these ncHLAp were immunogenic, meaning they could elicit an immune response from T cells. This is a crucial step in developing targeted immunotherapies for pancreatic cancer, as it shows that these cryptic antigens can be recognized and attacked by the immune system.
To further investigate the potential of these ncHLAp as targets for immunotherapy, the researchers tested their ability to activate T cells in vitro. They found that these cryptic antigens were able to activate T cells from both healthy individuals and patients with pancreatic cancer, indicating that they could be used to develop personalized cancer vaccines.
Overall, this study provides valuable insights into the role of the noncoding genome in cancer and the potential of ncHLAp as targets for T cell recognition in pancreatic cancer. Further research is needed to fully understand the mechanisms behind the generation and presentation of these cryptic antigens, and to develop effective immunotherapies targeting them.
Original Source: https://pubmed.ncbi.nlm.nih.gov/40339010/
