Immune organization in sentinel lymph nodes of melanoma patients is prognostic of distant metastases

Abstract

Sentinel lymph node (sLN) biopsy is part of melanoma staging, as involved LNs indicate a higher risk of recurrence. However, how the sLN is shaped by the tumor and reciprocally affects metastatic progression is poorly understood. Here, we mapped immune organization in involved and non-involved sLNs of 69 melanoma patients using high-resolution spatial proteomics, spatial transcriptomics and deep learning, leveraging the data for prognostic evaluation. In patients with involved LNs, a robust T cell response correlated with absence of recurrence. In non-involved LNs, protection from metastases was linked to expanded sinuses colocalized with plasmablasts whereas CCR7+ cells and Tregs correlated with future development of distant metastases. We trained a model that predicts development of distant metastases with 79% and 93% AUC for non-metastatic and metastatic LNs, respectively. Our findings reveal conserved immune patterns in sLNs that prospectively identify patients at risk for metastatic disease and may aid in therapeutic decisions.