Sensory nerves in melanoma impede the formation of tertiary lymphoid structures and anti-tumor immune responses
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA794351 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17442693_1.fastq.gz | Fastqsanger.gz | |||
| SRR17442693_2.fastq.gz | Fastqsanger.gz | |||
| SRR17442694_1.fastq.gz | Fastqsanger.gz | |||
| SRR17442694_2.fastq.gz | Fastqsanger.gz | |||
| SRR17442695_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Utilizing surgical and chemical skin sensory denervation methods, we show that afferent neurons support the growth of melanoma tumors in vivo. We demonstrate that sensory innervation limits the activation of effective anti-tumor immune response. Specifically, sensory ablation led to improved leukocyte recruitment and infiltration into tumors, decreased intratumoral lymphoid and myeloid immunosuppressive cells, and the activation of T effector cells within the TME. We found that cutaneous sensory nerves hinder the maturation of intratumoral high endothelial venules and the formation of mature tertriary lymphoid-like structures containing organized clusters of CD4+ T cells and B cells. Denervation further increased T cell clonality and expanded the B cell repertoire in the TME. Importantly, CD8a depletion prevented the denervation-dependent anti-tumor effects. Finally, we observed that the gene signatures associated with immune function and sensory innervation were inversely correlated in human primary cutaneous melanomas, and the latter was a negative prognostic marker of the overall survival in the examined cohort. Our results suggest that tumor-associated sensory neurons negatively regulate the development of effective anti-tumor immune responses, thereby defining a novel target for therapeutic intervention in the cancer setting.
2023-02-20 | GSE193065 | GEO
Project description:We identified sensory nerves as more abundant in triple-negative human breast tumors. Human triple negative breast cancer (TNBC) cells (MDA-MB-231, SUM159) were co-cultured with mice primary sensory neurons from dorsal root ganglia (DRG). Breast can-cer cells were found to attach to neurons and have higher migration speed and prolifera-tion rate. Species-specific RNA sequencing highlighted cell migration and adhesion among the most upregulated pathways for cancer cells in coculture. We identified a novel mechanism where cancer’s PlexinB3 interacted with neuron’s Sema5A to regulate attachment and migration along nerve fibers. These findings demonstrate that sensory nerves induced a drastic shift in TNBC cells gene expression, and that dirupting the nerve-cancer is a viable strategy to impede metastasis
2021-07-22 | GSE180508 | GEO
Project description:Peripheral neurons comprise a critical component of the tumor microenvironment (TME). The role of the autonomic innervation in cancer has been firmly established. However, the effect of the afferent (sensory) neurons on tumor progression remains unclear. Utilizing surgical and chemical skin sensory denervation methods, we showed that afferent neurons supported the growth of melanoma tumors in vivo and demonstrated that sensory innervation limited the activation of effective antitumor immune responses. Specifically, sensory ablation led to improved leukocyte recruitment into tumors, with decreased presence of lymphoid and myeloid immunosuppressive cells and increased activation of T-effector cells within the TME. Cutaneous sensory nerves hindered the maturation of intratumoral high endothelial venules and limited the formation of mature tertiary lymphoid-like structures containing organized clusters of CD4+ T cells and B cells. Denervation further increased T-cell clonality and expanded the B-cell repertoire in the TME. Importantly, CD8a depletion prevented denervation-dependent antitumor effects. Finally, we observed that gene signatures of inflammation and the content of neuron-associated transcripts inversely correlated in human primary cutaneous melanomas, with the latter representing a negative prognostic marker of patient overall survival. Our results suggest that tumor-associated sensory neurons negatively regulate the development of protective antitumor immune responses within the TME, thereby defining a novel target for therapeutic intervention in the melanoma setting.
| S-EPMC10314799 | biostudies-literature
Project description:Single-cell profiling of infiltrating B cells and tertiary lymphoid structures in the TME of gastric adenocarcinomas
2021-11-22 | GSE188895 | GEO
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
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 | GSE272410 | GEO
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
Project description:The functional effects of an RNA can arise from complex three-dimensional folds known as tertiary structures. However, predicting the tertiary structure of an RNA and whether an RNA adopts distinct tertiary conformations remains challenging. To address this, we developed BASH MaP, a single-molecule dimethyl sulfate (DMS) footprinting method and DAGGER, a computational pipeline, to identify alternative tertiary structures adopted by different molecules of RNA. BASH MaP utilizes potassium borohydride to reveal the chemical accessibility of the N7 position of guanosine, a key mediator of tertiary structures. We used BASH MaP to identify diverse conformational states and dynamics of RNA G-quadruplexes, an important RNA tertiary motif, in vitro and in cells. BASH MaP and DAGGER analysis of the fluorogenic aptamer Spinach reveals that it adopts alternative tertiary conformations which determine its fluorescence states. BASH MaP thus provides an approach for structural analysis of RNA by revealing previously undetectable tertiary structures.
2024-10-14 | GSE271825 | GEO
Project description:Infiltrating B cells and tertiary lymphoid structures in the TME
| PRJNA780577 | ENA
Project description:Peripheral nerve repair and functional recovery depend on the rate of nerve regeneration and the quality of target reinnervation. It is important to fully understand the cellular and molecular basis underlying the specificity of peripheral nerve regeneration, which means the achieving of respective correct pathfinding and accurate target reinnervation for regrowing motor and sensory axons. In this study, a quantitative proteomic technique, based on isobaric tags for relative and absolute quantitation (iTRAQ) was used to profile the protein expression pattern between single motor and sensory nerves at 14 days after peripheral nerve transection. Among a total of 1259 proteins identified, 176 proteins showed the differential expressions between injured motor and sensory nerves. Quantitative real-time RT-PCR and Western blot analysis were applied to validate the proteomic data on representative differentially expressed proteins. Functional categorization indicated that differentially expressed proteins were linked to a diverse array of molecular functions, including axonogenesis, response to axon injury, tissue remodeling, axon ensheathment, cell proliferation and adhesion, vesicle-mediated transport, response to oxidative stress, internal signal cascade, and macromolecular complex assembly, which might play an essential role in peripheral motor and sensory nerve regeneration. Overall, we hope that the proteomic database obtained in this study could serve as a solid foundation for the comprehensive investigation of differentially expressed proteins between injured motor and sensory nerves and for the mechanism elucidation of the specificity of peripheral nerve regeneration.
2020-12-10 | PXD022097 | Pride