Early Hepatic Lesions Display Immature Tertiary Lymphoid Structures and Show Elevated Expression of Immune Inhibitory and Immunosuppressive Molecules.
Clin Cancer Res
; 26(16): 4381-4389, 2020 08 15.
Article
en En
| MEDLINE
| ID: mdl-32269054
ABSTRACT
PURPOSE:
The impact of tertiary lymphoid structures (TLS) in hepatocellular carcinoma (HCC) progression is being extensively investigated. However, their presence during the early steps of human liver carcinogenesis remains unknown. We thus aimed to determine whether TLS are induced in preneoplastic/early hepatic lesions (EHL), and whether they are associated with a particular immune profile. EXPERIMENTALDESIGN:
A series of 127 EHLs (low/high-grade dysplastic nodules, early HCC, and small and progressed HCC) was included in the study. TLSs were investigated by pathologic reviewing. Densities of immune cells were assessed using IHC. A subset of lesions was microdissected and gene expression profiling was performed with a custom NanoString panel.RESULTS:
Compared with surrounding cirrhotic nodules, EHL of all stages displayed increased densities of T cells, B cells, and dendritic cells. Immature TLSs were identified in 24% of EHL. Gene expression profiling identified a subset of EHL with elevated mRNA levels of various cytokines involved in immune cells' recruitment and TLS induction. This subgroup of EHL also showed overexpression of genes related to T- and B-cells' activation and antigen presentation, as well as those related to immunosuppression and immune exhaustion.CONCLUSIONS:
Local immune activation occurs in the very early steps of liver carcinogenesis; however, it may not be fully efficient and paradoxically favor immune evasion and progression to full-blown HCC. These results have implications for the development of anti-HCC chemopreventive strategies in cirrhotic patients.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma Hepatocelular
/
Estructuras Linfoides Terciarias
/
Hígado
/
Neoplasias Hepáticas
Límite:
Aged
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2020
Tipo del documento:
Article
País de afiliación:
Francia