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Neoadjuvant immunotherapy promotes the formation of mature tertiary lymphoid structures in a remodeled pancreatic tumor microenvironment

ABSTRACT: Neoadjuvant immunotherapy promotes the formation of mature tertiary lymphoid structures in a remodeled pancreatic tumor microenvironment

PROVIDER: PRJNA1160822 | ENA |

REPOSITORIES: ENA

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Neoadjuvant immunotherapy promotes the formation of mature tertiary lymphoid structures in a remodeled pancreatic tumor microenvironment

Project description:Pancreatic adenocarcinoma (PDAC) is a rapidly progressing cancer that responds poorly to immunotherapies. Intratumoral tertiary lymphoid structures (TLS) have been associated with rare long-term PDAC survivors, but the role of TLS in PDAC and their spatial relationships within the context of the broader tumor microenvironment remain unknown. Here, we report the generation of a spatial multi-omics atlas of PDAC tumors and tumor-adjacent lymph nodes from patients treated with combination neoadjuvant immunotherapies. Using machine learning–enabled hematoxylin and eosin image classification models, imaging mass cytometry, and unsupervised gene expression matrix factorization methods for spatial transcriptomics, we characterized cellular states within and adjacent to TLS spanning across distinct spatial niches and pathologic responses. Unsupervised learning identified TLS-specific spatial gene expression signatures that significantly associated with improved survival in PDAC patients. We identified spatial features of pathologic immune responses, including intratumoral TLS–associated B-cell maturation colocalizing with IgG dissemination and extracellular matrix remodeling. Our findings offer insights into the cellular and molecular landscape of TLS in PDACs during immunotherapy treatment.

2025-08-12 | GSE277116 | GEO

Late-stage tertiary lymphoid structures in hepatocellular carcinoma treated with neoadjuvant immune checkpoint blockade [scRNA-seq]

Project description:Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade (ICB), but understanding of their clinical significance and the circumstances of their resolution remains incomplete. Here, we found that in hepatocellular carcinoma (HCC) treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse free survival. In areas of tumor regression, we further identified a non-canonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell-mature dendritic cell interactions, and increased expression of T cell memory markers. Collectively, these data suggest that TLS may serve be both a prognostic and predictive marker of response to immunotherapy in HCC and suggest a functional role for late-stage TLS T cell memory formation after elimination of viable tumor.

2024-09-13 | GSE272347 | GEO

Late-stage tertiary lymphoid structures in hepatocellular carcinoma treated with neoadjuvant immune checkpoint blockade [bulk RNA-seq]

2024-09-13 | GSE272346 | 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

Late-stage tertiary lymphoid structures in hepatocellular carcinoma treated with neoadjuvant immune checkpoint blockade

Project description:Late-stage tertiary lymphoid structures in hepatocellular carcinoma treated with neoadjuvant immune checkpoint blockade

| PRJNA1136490 | ENA

Late-stage tertiary lymphoid structures in hepatocellular carcinoma treated with neoadjuvant immune checkpoint blockade [scRNA-seq]

Project description:Late-stage tertiary lymphoid structures in hepatocellular carcinoma treated with neoadjuvant immune checkpoint blockade [scRNA-seq]

| PRJNA1136494 | ENA

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

Late-stage tertiary lymphoid structures in hepatocellular carcinoma treated with neoadjuvant immune checkpoint blockade [bulk RNA-seq]

Project description:Late-stage tertiary lymphoid structures in hepatocellular carcinoma treated with neoadjuvant immune checkpoint blockade [bulk RNA-seq]

| PRJNA1136492 | ENA

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