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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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			Action	DRS
	SRR28067220.fastq.gz	Fastqsanger.gz
	SRR28067221.fastq.gz	Fastqsanger.gz
	SRR28067222.fastq.gz	Fastqsanger.gz
	SRR28067223.fastq.gz	Fastqsanger.gz
	SRR28067224.fastq.gz	Fastqsanger.gz

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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.

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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.

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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

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Denunded HUVEC/HUASMC spheroids vs. HUASMC spheroids

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

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