表达 PD-L1 的 NK 细胞预测神经母细胞瘤的良好预后及对 PD-1/PD-L1 阻断的应答

T/NK cell-based immunotherapy has achieved remarkable success in adult cancers but has limited efficacy in pediatric malignancies including high-risk neuroblastoma (NB). Immune defects of NB tumor microenvironment are poorly understood compared with adults.

Here, we described the unique characteristics of NB immune contexture and determined the phenotype signatures of PD-L1-expressing CD8 + T and NK cells in NB tumors by systemically analyzing the spatial distribution of T and NK cells and the distinct expression of programmed death 1 (PD-1) and its ligand (PD-L1) in patients with NB.

We found that PD-L1-expressing CD8 + T and NK cells in NB tumors were highly activated and functionally competent and associated with better clinical outcomes. Intratumoral NK cells were a favorable prognostic biomarker independent of CD8 + T cells, PD-1/PD-L1 expression, tumor stage, MYCN amplification, and risk classification.

NK cells combined with anti-PD-1/PD-L1 antibodies showed potent antitumor activity against both MYCN -amplified and non-amplified NBs in vitro and in vivo , and PD-L1-expressing NK cells associated with improved antitumor efficacy. Collectively, we raise novel insights into the role of PD-L1 expression on CD8 + T-cell and NK-cell activation.

We highlight the great potential of intratumoral NK cells in better defining risk stratification, and predicting survival and response to anti-PD-1/PD-L1 therapy in NB.

These findings explain why single anti-PD-1/PD-L1 therapy may not be successful in NB, suggesting its combination with NK cell-adoptive cellular therapy as a promising strategy for relapsing/refractory NB.

This study provides a potential prospect that patients with PD-L1-expressing NK cells may respond to anti-PD-1/PD-L1 therapy.