Spatial transcriptomics unveils immune cellular ecosystems associated with patient survival in diffuse large B-cell...

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Diffuse Large B-cell Lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma, but current treatments are limited by tumor heterogeneity and complex immune microenvironments.
• Understanding the spatial organization of malignant and immune cells within the DLBCL tumor microenvironment (TME) is crucial for improving therapeutic strategies and patient outcomes.

Purpose of the Study:

• To investigate the spatial organization of cellular ecosystems within the DLBCL TME using spatial transcriptomics.
• To identify how spatial context and cell-cell interactions influence immune function and clinical outcomes in DLBCL.
• To develop prognostic biomarkers based on spatial architecture.

Main Methods:

• Pilot spatial transcriptomics analysis of primary DLBCL tissue sections.
• Identification and characterization of distinct, spatially organized cellular ecosystems (Cell-Eco).
• Validation of key cellular features at the protein level and assessment of prognostic value using gene signatures in independent patient cohorts.

Main Results:

• Six recurrent, spatially organized cellular ecosystems (Cell-Eco) were identified, each with unique immune cell composition, transcriptional programs, and neighborhood architectures.
• Spatial context and local interactions, rather than immune cell frequency alone, were found to shape immune function and clinical associations within the DLBCL TME.
• Tumor-associated macrophages were identified as key spatial partners of malignant B cells, significantly influencing TME structure.

Conclusions:

• Spatial transcriptomics provides a framework for understanding immune organization in DLBCL.
• Cell-Eco gene signatures derived from spatial architecture can robustly stratify DLBCL patient survival.
• Tumor cellular architecture is a critical determinant of immune function and prognosis in DLBCL.