Spatial profiling uncovers multicellular dynamics in early relapse of hepatitis B virus-associated follicular lymphoma.

Hepatitis B virus (HBV) infections are associated with an increased risk of B-cell lymphomas, including follicular lymphoma (FL). Chronic HBV infection and shifts in infection status following treatment can influence lymphomagenesis and immune reprogramming, potentially affecting clinical outcomes. Using the CosMx Spatial Molecular Imaging, after integrated with dynamic HBV infection states and duration of overt infection, this refines four recurrent patterns, especially memory B cell-like malignant cells (MBLM) subtype (PTPRCAP + ) that is traced with atypical features and latent indolence, and virus protein transport-related follicular dendritic cell (FDC) which shows interplay with MBLM. Except for virus-induced immune exhaustion, distinct contributions to POD24 occurrence from malignant cells and immunosuppressive cell communities under distinct HBV infection states are discerned such as through CCL21/CCR7 signaling pathway. Taken together, our spatial multicellular dynamics reveal an increased prevalence of MBLM and variable FDC phenotypes which is associated with POD24 occurrence in HBV-related FL tumors.