Background Patients with cancers that exhibit extraordinarily high somatic mutation numbers are ideal candidates for immunotherapy and enable identifying tumor-specific peptides through stimulation of tumor-reactive T cells Tc.
Finally, cytotoxicity against autologous tumor cells was assessed in a degranulation assay. Results tumor-specific candidate peptides—97 cryptic peptides and 3 classically mutated neoantigens—were selected. Stimulation of pTc and TiTc with neoantigens and selected cryptic peptides resulted in increased release of cytotoxic granules in the presence of autologous tumor cells, substantiating their improved tumor cell recognition.
Subpopulation analysis prior to peptide stimulation revealed that pTc mainly consisted of memory Tc, whereas TiTc constituted primarily of effector and effector memory Tc.
This allows to infer that TiTc reacting to neoantigens and cryptic peptides must be present within the tumor microenvironment. Moreover, stimulation with these peptides significantly strengthened tumor cell recognition by Tc. Since the overall number of neoantigenic peptides identifiable by HLA ligandome analysis hitherto is small, our data emphasize the relevance of increasing the target scope for cancer vaccines by the cryptic peptide category.
Data are available in a public, open access repository. You will be able to get a quick price and instant permission to reuse the content in many different ways. Tumor-specific peptides presented via HLA class I molecules are obvious candidates for cancer vaccine designs. HLA ligandome analyses are the only way to identify cryptic peptides translated from genomic regions, presumed to not be translated—in addition to the classical mutation-derived neoantigens.
