APOBEC3B stratifies ovarian clear cell carcinoma with distinct immunophenotype and prognosis.
Br J Cancer
; 128(11): 2054-2062, 2023 06.
Article
en En
| MEDLINE
| ID: mdl-36997661
ABSTRACT
BACKGROUND:
Ovarian clear cell carcinoma (OCCC) is a challenging disease due to its intrinsic chemoresistance. Immunotherapy is an emerging treatment option but currently impeded by insufficient understanding of OCCC immunophenotypes and their molecular determinants.METHODS:
Whole-genome sequencing on 23 pathologically confirmed patients was employed to depict the genomic profile of primary OCCCs. APOBEC3B expression and digital pathology-based Immunoscore were assessed by performing immunohistochemistry and correlated with clinical outcomes.RESULTS:
An APOBEC-positive (APOBEC+) subtype was identified based on the characteristic mutational signature and prevalent kataegis events. APOBEC + OCCC displayed favourable prognosis across one internal and two external patient cohorts. The improved outcome was ascribable to increased lymphocytic infiltration. Similar phenomena of APOBEC3B expression and T-cell accumulation were observed in endometriotic tissues, suggesting that APOBEC-induced mutagenesis and immunogenicity could occur early during OCCC pathogenesis. Corroborating these results, a case report was presented for an APOBEC + patient demonstrating inflamed tumour microenvironment and clinical response to immune checkpoint blockade.CONCLUSIONS:
Our findings implicate APOBEC3B as a novel mechanism of OCCC stratification with prognostic value and as a potential predictive biomarker that may inform immunotherapeutic opportunities.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
/
Carcinoma
/
Adenocarcinoma de Células Claras
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Br J Cancer
Año:
2023
Tipo del documento:
Article
País de afiliación:
China