Negative trade-off between neoantigen repertoire breadth and the specificity of HLA-I molecules shapes antitumor immunity.
Nat Cancer
; 2(9): 950-961, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-35121862
ABSTRACT
Human leukocyte antigen class I (HLA-I) genes shape our immune response against pathogens and cancer. Certain HLA-I variants can bind a wider range of peptides than others, a feature that could be favorable against a range of viral diseases. However, the implications of this phenomenon on cancer immune response are unknown. Here we quantified peptide repertoire breadth (or promiscuity) of a representative set of HLA-I alleles and found that patients with cancer who were carrying HLA-I alleles with high peptide-binding promiscuity have significantly worse prognosis after immune checkpoint inhibition. This can be explained by a reduced capacity of the immune system to discriminate tumor neopeptides from self-peptides when patients carry highly promiscuous HLA-I variants, shifting the regulation of tumor-infiltrating T cells from activation to tolerance. In summary, HLA-I peptide-binding specificity shapes neopeptide immunogenicity and the self-immunopeptidome repertoire in an antagonistic manner, and could underlie a negative trade-off between antitumor immunity and genetic susceptibility to viral infections.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Antígenos de Histocompatibilidad Clase I
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Nat Cancer
Año:
2021
Tipo del documento:
Article
País de afiliación:
Hungria