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Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer

ABSTRACT: Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer

PROVIDER: PRJNA732692 | ENA |

REPOSITORIES: ENA

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Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer

Project description:The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of B cell responses within TLS in renal cell carcinoma (RCC). B cells were enriched in TLS, and therein, we could identify all B cell maturation stages toward plasma cell (PC) formation. B cell repertoire analysis revealed clonal diversification, selection, expansion in TLS, and the presence of fully mature clonotypes at distance. In TLS+ tumors, IgG- and IgA-producing PCs disseminated into the tumor beds along fibroblastic tracks. TLS+ tumors exhibited high frequencies of IgG-producing PCs and IgG-stained and apoptotic malignant cells, suggestive of anti-tumor effector activity. Therapeutic responses and progression-free survival correlated with IgG-stained tumor cells in RCC patients treated with immune checkpoint inhibitors. Thus, intratumoral TLS sustains B cell maturation and antibody production that is associated with response to immunotherapy, potentially via direct anti-tumor effects.

2022-03-03 | GSE175540 | GEO

Infiltrating B cells and tertiary lymphoid structures in the TME

Project description:Single-cell profiling of infiltrating B cells and tertiary lymphoid structures in the TME of gastric adenocarcinomas

2021-11-22 | GSE188895 | GEO

Immunotherapeutic antibodies derived from human tumor tertiary lymphoid structures

Project description:We report that intratumoral Tertiary Lymphoid Structures (TLS) in human ovarian cancer contain highly oligoclonal B cells that produce IgA and IgG. Using a recombinant antibody cloned from the dominant sequence of an ovarian cancer TLS, we abrogated the growth of the autologous human tumor in vivo, through recognition of the extracellular domain of tumor-promoting GPR85. TLS-derived antibodies therefore contribute to anti-tumor immunity, which could be leveraged for novel immunotherapies.

2026-06-12 | PXD036740 | Pride

Gut-Resident IL10+CX3CR1hi Macrophages Induce Tertiary Lymphoid Structures and IgA Response in Situ

Project description:Gut resident IL10+CX3CR1hi macrophages drive development of mucosal tertiary lymphoid structures that serve as ectopic site of the IgA response to enteric infection.

2020-04-17 | GSE121471 | GEO

Molecular and spatial analysis unveils the functional basis of tertiary lymphoid structures in Sjogren’s syndrome[scRNA-seq]

Project description:The key role of tertiary lymphoid structures in autoimmune and non-autoimmune conditions has been recently appreciated. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, their cellular sources and temporal and spatial relationship remain unknown. Using single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren’s disease and Sicca Syndrome, ex-vivo and in vivo functional studies, we construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures. We confirm the presence of a fibroblast cell state and identify an undescribed pericyte/mural cell state with potential immunological functions. The identification of novel cellular properties associated with these structures and the molecular and functional interactions identified by this analysis provide key therapeutic cues for tertiary lymphoid structures associated conditions in autoimmunity and cancer.

2024-07-17 | GSE272409 | GEO

Molecular and spatial analysis unveils the functional basis of tertiary lymphoid structures in Sjogren’s syndrome[bulk RNA-seq]

2024-07-17 | GSE272410 | GEO

Nociceptive innervation limits tertiary lymphoid structures to promote lung cancer

Project description:Nociceptive innervation limits tertiary lymphoid structures to promote lung cancer

| PRJNA1290269 | ENA

Infiltrating B cells and tertiary lymphoid structures in the TME

Project description:Infiltrating B cells and tertiary lymphoid structures in the TME

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Loss of Vascular Endothelial Notch Signaling Induces Tertiary Lymphoid Structures in the Kidney

Project description:Tertiary lymphoid structures (TLS are lymph node-like immune cell clusters that emerge during chronic inflammation in non-lymphoid organs like the kidney, but their origin remains not well understood. Here we show, using conditional deletion strategies of the canonical Notch signaling mediator Rbpj, that loss of endothelial Notch signaling in adult mice induces the spontaneous formation of bona fide TLS in the kidney, liver and lung, based on molecular, cellular and structural criteria. These TLS form in a stereotypical manner around parenchymal arteries, while secondary lymphoid structures remained largely unchanged. This effect is mediated by endothelium of blood vessels, but not lymphatics, since a lymphatic endothelial-specific targeting strategy did not result in TLS formation, and involves loss of arterial specification and concomitant acquisition of a high endothelial cell phenotype, as shown by transcriptional analysis of kidney endothelial cells. This indicates a so far unrecognized role for vascular endothelial cells and Notch signaling in TLS initiation.

2022-02-24 | GSE193544 | GEO

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

Project description: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.

2024-09-11 | GSE206245 | GEO

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