Biomarker analysis from a phase II multi-institutional study of nivolumab in patients with advanced refractory biliary tract cancer.
Eur J Cancer
; 176: 171-180, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-36252287
ABSTRACT
BACKGROUND:
Our previous phase II study demonstrated that nivolumab provides modest but durable clinical efficacy in patients with refractory biliary tract cancer, suggesting the significant clinical benefit of nivolumab in selected patients and the necessity of predictive biomarkers. We evaluated clinicopathological characteristics and tumour microenvironment of the patients who were enrolled the trial to identify potential biomarkers.METHODS:
Baseline clinicopathological characteristics and pretreatment tumour samples were collected. The obtained tumour samples were assessed for whole exome sequencing, RNA sequencing and immunohistochemistry. Their correlations with clinical outcome were analysed.RESULTS:
Pretreatment tumour evaluation revealed PD-L1 expression on tumour, CD8 T cell infiltration and high ratio of CD8 T cell/regulatory T cell in tumour microenvironment were significantly associated with prolonged progression-free survival (PFS), while PD-1 expression on lymphocytes and CD68 macrophages infiltration in tumour microenvironment had no predictive role. Asian patients (N = 3) had improved PFS and disease control rate compared with non-Asian (N = 54). A six-gene predictive model was constructed by evaluation of total 23,550 candidate genes from RNA sequencing of baseline tumour samples using LASSO-Cox regression analysis, and high score of the six-gene prediction model was associated with prolonged PFS.CONCLUSION:
This study suggests that PD-L1 expression on tumour, CD8 T cell infiltration and high ratio of CD8/regulatory T cells and six-gene expression profile in tumour microenvironment may be potential predictive biomarkers of nivolumab in biliary tract cancers. Further studies are needed to confirm these findings.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Sistema Biliar
/
Antineoplásicos Imunológicos
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article