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Researchers investigated how EBV-positive diffuse large B-cell lymphoma evades immune responses through PD-L1-mediated mechanisms. Using spatial transcriptomics, proteomics, and single-cell sequencing, they discovered that tumors with PD-L1 gains allow T cells to accumulate nearby but prevent direct contact through cancer-associated fibroblasts at tumor boundaries. This creates a multilayered immune suppression system involving physical exclusion, metabolic constraints, and T-cell exhaustion that blocks effective anti-tumor immunity.
Why it matters
These findings explain a key mechanism by which an aggressive lymphoma escapes immune surveillance despite T-cell infiltration, potentially informing more effective immunotherapy strategies that target not just PD-L1 but also the fibroblast barrier and metabolic suppression pathways in EBV-positive DLBCL patients.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
EBV-positive diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma enriched in elderly patients, in which PD-L1 genomic gains cooperate with viral signalling to promote immune escape. However, the spatial mechanisms by which PD-L1 reshapes the tumour microenvironment remain unresolved. Here, we integrate genomic profiling with spatial transcriptomics, spatial proteomics, and single-cell RNA sequencing to resolve the tumour-immune architecture of EBV-positive DLBCL. PD-L1 gain tumours exhibit a striking decoupling of immune proximity and immune engagement: T cells accumulate in close proximity to tumour cells yet direct tumour-immune contact is largely absent. Tumour boundaries are enriched for cancer-associated fibroblasts and display transcriptional signatures of metabolic immune suppression, while tumour-proximal T cells exhibit pronounced exhaustion. Together, these findings reveal a PD-L1 driven spatial immune evasion architecture that permits immune infiltration while enforcing multilayered suppression through fibroblast-mediated exclusion, metabolic constraint, and T-cell dysfunction, ultimately preventing effective anti-tumour immunity in EBV-positive DLBCL.
Source: PD-L1-linked spatial decoupling of tumour-immune interactions in EBV-positive DLBCL