摘要 : Immune checkpoint blockade (ICB) using anti-PD-1/PD-L1 and anti-CTLA-4 antibodies significantly enhances survival in metastatic melanoma patients and has recently been shown to prolong relapse-free survival in stage III and high-r... 展开 Immune checkpoint blockade (ICB) using anti-PD-1/PD-L1 and anti-CTLA-4 antibodies significantly enhances survival in metastatic melanoma patients and has recently been shown to prolong relapse-free survival in stage III and high-risk stage II melanoma patients (Eggermont et al., 2018; Luke et al., 2022; Robert et al., 2015). However, a significant proportion of patients does not respond to ICB prior to or following surgery, for reasons incompletely understood. We and others recently identified tumor-draining lymph nodes (TDLNs) to be critically involved in anti-PD-L1 treatment efficacy in preclinical tumor models (Dammeijer et al., 2020; Fransen et al., 2018). Furthermore, we found that abundant PD-1 andPD-L1 interactions in TDLNs of patients with non-met -astatic melanoma at presentation were associated with distant disease recurrence, suggesting that immune suppression in TDLNs might prevent a durable and effective systemic anti-tumor immune response. However, it remains incompletely understood which cells and pathways-including their spatial tissue localization-within TDLNs promote disease recurrence in melanoma. Here, we address these issues by analyzing the immune composition in TDLNs of stage III melanoma patients using multiplexed gene expression analysis, digital spatial profiling (DSP), and multi-color confocal imaging. 收起