Proteogenomic analysis identifies neoantigens and bacterial peptides as immunotherapy targets in colorectal cancer.
Pharmacol Res
; 204: 107209, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38740147
ABSTRACT
Considerable progress has recently been made in cancer immunotherapy, including immune checkpoint blockade, cancer vaccine, and adoptive T cell methods. The lack of effective targets is a major cause of the low immunotherapy response rate in colorectal cancer (CRC). Here, we used a proteogenomic strategy comprising immunopeptidomics, whole exome sequencing, and 16â¯S ribosomal DNA sequencing analyses of 8 patients with CRC to identify neoantigens and bacterial peptides that can serve as antitumor targets. This study directly identified several personalized neoantigens and bacterial immunopeptides. Immunoassays showed that all neoantigens and 5 of 8 bacterial immunopeptides could be recognized by autologous T cells. Additionally, T cell receptor (TCR) αß sequencing revealed the TCR repertoire of epitope-reactive CD8+ T cells. Functional studies showed that T cell receptor-T (TCR-T) could be activated by epitope pulsed lymphoblastoid cells. Overall, this study comprehensively profiled the CRC immunopeptidome, revealing several neoantigens and bacterial peptides with potential to serve as immunotherapy targets in CRC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Proteogenomics
/
Immunotherapy
/
Antigens, Neoplasm
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Pharmacol Res
Journal subject:
FARMACOLOGIA
Year:
2024
Type:
Article
Affiliation country:
China