Single-cell-type Spatial Proteomics Unveils Precision Medicine Insights in Composite Small Lymphocytic and Classical Hodgkin Lymphoma

Deep Visual Proteomics (DVP) is an innovative technique that enables spatially resolved sing-cell-type proteome analysis. The coexistence of classical Hodgkin lymphoma (cHL) and small lymphocytic lymphoma (SLL) in a single patient presents a challenging scenario for clinical decision-making. In this study, we investigate the potential of DVP to provide insights into precision medicine strategies. We use DVP to comprehensively profile the proteomic landscapes and signaling pathways within cHL and SLL compartments in a 71-year-old woman with composite lymphoma. Our analysis reveals distinct proteome profiles in cHL and SLL populations, highlighting their clonal unrelatedness. Beyond ABVD chemotherapy, we identify subtype-specific therapeutic targets: Minichromosome Maintenance protein inhibitors and proteasome inhibitors for cHL, and H3K27 methylation inhibitors and receptor tyrosine kinase inhibitors for SLL. Additionally, we explore interleukin-4 inhibition as a potential strategy to manage chemo-resistance. DVP provides insights into spatial single-cell proteomics, guiding personalized treatments for composite lymphoma patients.