Hepatitis B virus (HBV) infection increases the risk for B-cell lymphomas including follicular lymphoma (FL). HBV-positive patients have a higher incidence of disease progression with 24 months (POD24) and precisely identifying those patients with potential POD24 remains a challenge. Therefore, we reconstructed the spatial molecular crosstalk in HBV-associated tumors with POD24 after immunochemotherapy using spatial transcriptomics at single-cell resolution. The tumors from patients with dynamic HBV states and distinct virus carrying times were characterized by refined four malignant cell subsets and four follicular dendritic cell (FDC) subsets, including a newly identified memory B cell-like malignant cells (MBLM) subset that was traced as atypical malignant cells with latent indolence, prominently occurred in HBV-high tumors and increased following POD24 occurrence. The newly-identified virus protein transport-related FDC differed significantly in tumors with dynamic HBV states and was negatively correlated with MBLM. Stratified by dynamic HBV states, specific immunosuppressive cell cohorts colocalized with certain malignant cells may interpret the POD24 occurrence which was associated with virus-induced immune exhaustion. Our spatial molecular classifications and multicellular stratifications revealed an intratumoral crosstalk between dominant malignant cells subsets and immune cells which may promote POD24 occurrence in HBV-related FL tumors, and provided therapeutic targeting of specific cellular molecules.
No relevant conflicts of interest to declare.
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal