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Patient-derived lymphoma spheroids integrating immune tumor microenvironment as preclinical follicular lymphoma models for personalized medicine

ABSTRACT: Patient-derived lymphoma spheroids integrating immune tumor microenvironment as preclinical follicular lymphoma models for personalized medicine

PROVIDER: PRJNA1079718 | ENA |

REPOSITORIES: ENA

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Patient-derived lymphoma spheroids integrating immune tumor microenvironment as preclinical follicular lymphoma models for personalized medicine

Project description:Background Follicular lymphoma (FL), the most common indolent non-Hodgkin’s Lymphoma, is a heterogeneous disease and a paradigm of the contribution of immune tumor microenvironment to disease onset, progression, and therapy resistance. Patient-derived models are scarce and fail to reproduce immune phenotypes and therapeutic responses. Methods To capture disease heterogeneity and microenvironment cues, we developed a patient-derived lymphoma spheroid (FL-PDLS) model culturing FL cells from lymph nodes (LN) with an optimized cytokine cocktail that mimics LN stimuli and maintains tumor cell viability. Results FL-PDLS, mainly composed of tumor B cells (60% on average) and autologous T cells (13% CD4 and 3% CD8 on average, respectively), rapidly organizes into patient-specific three-dimensional (3D) structures of three different morphotypes according to 3D imaging analysis. RNAseq analysis indicates that FL-PDLS reproduces FL hallmarks with the overexpression of cell cycle, BCR, or mTOR signaling related gene sets. FL-PDLS also recapitulates the exhausted immune phenotype typical of FL-LN, including expression of BTLA, TIGIT, PD-1, TIM-3, CD39 and CD73 on CD3+ T cells. These features render FL-PDLS an amenable system for immunotherapy testing. With this aim, we demonstrate that the combination of obinutuzumab (anti-CD20) and nivolumab (anti-PD1) reduces tumor load in a significant proportion of FL-PDLS. Interestingly, B cell depletion inversely correlates with the percentage of CD8+ cells positive for PD-1 and TIM-3. Conclusions In summary, FL-PDLS is a robust patient-derived 3D system that can be used as a tool to mimic FL pathology and to test novel immunotherapeutic approaches in a context of personalized medicine.

2024-02-28 | GSE256457 | GEO

Single-cell-type Spatial Proteomics Unveils Precision Medicine Insights in Composite Small Lymphocytic and Classical Hodgkin Lymphoma

Project description:Deep Visual Proteomics (DVP) is an innovative technique that enables spatially resolved sing-cell-type proteome analysis. The coexistence of classical Hodgkin lymphoma (cHL) and small lymphocytic lymphoma (SLL) in a single patient presents a challenging scenario for clinical decision-making. In this study, we investigate the potential of DVP to provide insights into precision medicine strategies. We use DVP to comprehensively profile the proteomic landscapes and signaling pathways within cHL and SLL compartments in a 71-year-old woman with composite lymphoma. Our analysis reveals distinct proteome profiles in cHL and SLL populations, highlighting their clonal unrelatedness. Beyond ABVD chemotherapy, we identify subtype-specific therapeutic targets: Minichromosome Maintenance protein inhibitors and proteasome inhibitors for cHL, and H3K27 methylation inhibitors and receptor tyrosine kinase inhibitors for SLL. Additionally, we explore interleukin-4 inhibition as a potential strategy to manage chemo-resistance. DVP provides insights into spatial single-cell proteomics, guiding personalized treatments for composite lymphoma patients.

2024-10-29 | PXD051795 | Pride

Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

Project description:This SuperSeries is composed of the following subset Series: GSE29996: Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine [Affymetrix SNP array data] GSE29998: Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine [Illumina mRNA expression array data] Refer to individual Series

2012-10-25 | E-GEOD-29999 | biostudies-arrayexpress

IGNITE: Genomic Medicine Implementation - The Personalized Medicine Program

Project description:IGNITE: Genomic Medicine Implementation - The Personalized Medicine Program

| PRJNA606620 | ENA

IGNITE: Genomic Medicine Implementation - The Personalized Medicine Program

Project description:IGNITE: Genomic Medicine Implementation - The Personalized Medicine Program

| PRJNA606621 | ENA

First-in-human clinical trial of personalized neoantigen vaccines as early intervention in untreated patients with lymphoplasmacytic lymphoma

Project description:We performed single cell RNA-seq gene expression analysis on bone marrow of 9 lymphoplasmacytic lymphoma patients before and after vaccination with personalized idiotype DNA vaccine to study changes in tumor microenvironment

2023-09-20 | GSE243545 | GEO

Integrating multisector molecular characterization into personalized peptide vaccine design for patients with newly diagnosed glioblastoma.

Project description:Integrating multisector molecular characterization into personalized peptide vaccine design for patients with newly diagnosed glioblastoma.

| PRJNA997365 | ENA

Denunded HUVEC/HUASMC spheroids vs. HUASMC spheroids

Project description:Denunded HUVEC/HUASMC spheroids vs. HUASMC spheroids

| PRJNA657248 | ENA

Integrating Patient Perspectives into Personalized Medicine in Idiopathic Pulmonary Fibrosis.

Project description:Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease which has a major impact on patients' quality of life (QOL). Except for lung transplantation, there is no curative treatment option. Fortunately, two disease-modifying drugs that slow down disease decline were recently approved. Though this is a major step forward, these drugs do not halt or reverse the disease, nor convincingly improve health-related QOL. In daily practice, disease behavior and response to therapy greatly vary among patients. It is assumed that this is related to the multiple biological pathways and complex interactions between genetic, molecular, and environmental factors that are involved in the pathogenesis of IPF. Recently, research in IPF has therefore started to focus on developing targeted therapy through identifying genetic risk factors and biomarkers. In this rapidly evolving field of personalized medicine, patient factors such as lifestyle, comorbidities, preferences, and experiences with medication should not be overlooked. This review describes recent insights and methods on how to integrate patient perspectives into personalized medicine. Furthermore, it provides an overview of the most used patient-reported outcome measures in IPF, to facilitate choices for both researchers and clinicians when incorporating the patient voice in their research and care. To enhance truly personalized treatment in IPF, biology should be combined with patient perspectives.

| S-EPMC5742327 | biostudies-other

Gene epression profile of s-spheroids and t-spheroids differentiated from iPS cells

Project description:For definitive endoderm differentiation, iPS cells (day0) were treated with 100 ng ml-1 activin A and 3μM CHIR99021 for 1 day and 100 ng ml-1 activin A for the following two days. Definitive endoderm was subsequently treated with 3uM CHIR99021 and 500ng ml-1 FGF4 for mid/hindgut differentiation. Mid/hindgut floating spheroids (fl; t-Spheroids) were collected from culture medium from day6 to day 8. On day6, mid/hindgut cells were dissociated into single cells and seeded onto EZSPHERE plate to generate suspension spheroids(EZ; s-Spheroids). RNA of fl spheroids and EZ spheroids were extracted using QIAGEN RNeasy kit.

2022-11-15 | GSE182230 | GEO

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