Macrophage-mediated anti-tumor immunity against high-risk neuroblastoma.
Genes Immun
; 23(3-4): 129-140, 2022 06.
Article
em En
| MEDLINE
| ID: mdl-35525858
ABSTRACT
Neuroblastoma is the most common extracranial childhood solid tumor. The majority of high-risk neuroblastoma is resistant/refractory to the current high intensity therapy. Neuroblastoma lacks classical HLA Class I expression and exhibits low mutation burden, allowing neuroblastoma cells to evade CD8+ T cell-mediated immunity. Neuroblastoma cells do not express PD-L1, and tumor-associated macrophages are the predominant PD-L1+ cells in the tumor. In this study, we performed gene expression profiling and survival analyses on large neuroblastoma datasets to address the prognostic effect of PD-L1 gene expression and the possible involvement of the SLAMF7 pathway in the anti-neuroblastoma immunity. High-level expression of PD-L1 was found significantly associated with better outcome of high-risk neuroblastoma patients; two populations of PD-1+ PD-L1+ macrophages could be present in high-risk tumors with PD-1/PD-L1 ratios, ≈1 and >1. Patients with the PD-1/PD-L1 ratio >1 tumor showed inferior survival. High-level co-expression of SLAMF7 and SH2D1B was significantly associated with better survival of the high-risk neuroblastoma patients. Together, this study supports the hypothesis that macrophages are important effector cells in the anti-high-risk neuroblastoma immunity, that PD-1 blockade therapy can be beneficial to the high-risk neuroblastoma subset with the PD-1/PD-L1 expression ratio >1, and that SLAMF7 is a new therapeutic target of high-risk neuroblastoma.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígeno B7-H1
/
Macrófagos
/
Neuroblastoma
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Genes Immun
Ano de publicação:
2022
Tipo de documento:
Article