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Single-Cell and Spatial Transcriptome Analyses Reveal Tertiary Lymphoid Structures Linked to Tumour Progression and Immunotherapy Response in Nasopharyngeal Carcinoma

ABSTRACT: Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE206245 | GEO | 2024/09/11

REPOSITORIES: GEO

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Single-Cell and Spatial Transcriptome Analyses Reveal Tertiary Lymphoid Structures Linked to Tumour Progression and Immunotherapy Response in Nasopharyngeal Carcinoma

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