Spatial Transcriptomics of Lymph Node Architecture in Nigerian Patients with Diffuse Large B Cell Lymphoma: An Original Tumour Microenvironment Analysis

This dissertation applies spatial transcriptomics to characterise lymph node tumour microenvironment (TME) architecture in Nigerian patients with diffuse large B cell lymphoma (DLBCL), developing an original spatial TME framework that links microenvironmental composition to clinical outcome in this understudied African lymphoma population. DLBCL is the most common lymphoma in Nigeria and shows distinct molecular and clinical characteristics compared to European cohorts, yet no spatial transcriptomics investigation has been conducted in any Nigerian lymphoma series. Formalin-fixed paraffin-embedded lymph node biopsies from 60 newly diagnosed DLBCL patients at University College Hospital Ibadan, Lagos University Teaching Hospital, and Federal Medical Centre Owerri were selected. Visium spatial gene expression profiling was performed using 10x Genomics Visium CytAssist platform. Cell type deconvolution was performed by integration with single-cell reference maps. Spatial clustering analysis identified distinct TME niches. Key findings included identification of a novel Macrophage-Exhausted T Cell Co-Enriched Spatial Domain (METACD) present in 43 percent of DLBCL samples, characterised by spatial co-localisation of CD163+ tumour-associated macrophages and PD-1+LAG3+ exhausted T cells, associated with significantly shorter progression-free survival (median 9.2 vs 24.7 months). Cell-cell communication analysis revealed a novel SPP1-MET signalling axis operating within METACD niches. An original Spatial DLBCL Microenvironment Classification incorporating METACD status is proposed as a prognostic biomarker. Keywords: spatial transcriptomics, DLBCL, tumour microenvironment, lymphoma, Nigeria.