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Follicular lymphoma microenvironment characteristics associated with tumor cell mutations and MHC class II expression

ABSTRACT: Follicular lymphoma (FL) is a B-cell lymphoma with a complex tumor microenvironment that is rich in non-malignant immune cells. We applied single-cell RNA-sequencing to characterize the immune microenvironment of FL. This provides a classification framework of the FL microenvironment, their association with FL genotypes and antigen presentation, and informs different potential immunotherapeutic strategies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE203610 | GEO | 2022/05/28

REPOSITORIES: GEO

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Microenvironment subtypes and association with tumor cell mutations and antigen expression in follicular lymphoma

Project description:Follicular lymphoma (FL) is a B-cell lymphoma with a complex tumor microenvironment that is rich in non-malignant immune cells. We applied single-cell RNA-sequencing to characterize the immune microenvironment of FL. This provides a classification framework of the FL microenvironment, their association with FL genotypes and antigen presentation, and informs different potential immunotherapeutic strategies.

| EGAS00001006052 | EGA

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

Abberant Cathepsin S Activity Modulates the Immune Microenvironment in Follicular Lymphoma

Project description:Tumor cells can induce their own advantageous microenvironment. Here, we describe aberrant cathepsin S (CTSS) activity to modulate T-cell activation in follicular lymphoma (FL). In donor-derived FLs following bone marrow transplantation, we identified independent acquisition of CTSS mutations at Y132 in the donor´s and recipient's tumors. In a larger cohort, 6% of FL (20/312) harbored CTSS mutations, mostly Y132D, another 14% had CTSS amplification (40/280). Y132D leads to accelerated conversion from pro-CTSS to active CTSS and increased substrate cleavage, including CD74, which regulates MHC-II restricted antigen-presentation. In co-culture experiments, CTSS mutant lymphoma cells induced increased antigen-specific CD4+ T-cell activation. Moreover, antigen-processing was the top upregulated pathway in CTSS mutant primary FL biopsies. Thus, aberrant CTSS activity is a promising target in lymphoma.

2021-01-07 | PXD014612 | Pride

Gene expression Profiling in Follicular Lymphomas

2014-07-01 | GSE55267 | GEO

Gene expression profiling in follicular lymphoma (FL) samples and paired transformed follicular lymphoma (tFL) (n=6 samples)

Project description:Follicular lymphoma (FL) is the second most common forms of B cell lymphoma that result from the expansion of germinal center (GC) B cells. Here, we aimed to find differential expression of genes between patient samples isolated from indoent FL or transformed and aggressive FL.

2019-12-20 | GSE142334 | GEO

Gene expression Profiling in Follicular Lymphomas

Project description:Follicular lymphoma (FL) is an indolent, but incurable subtype of non-Hodgkin lymphoma. These tumor harbor t (14;18) translocation in at least 90% of patients. Recently, activating EZH2 mutations have been Follicular lymphoma (FL) is an indolent, but incurable subtype of non-Hodgkin lymphoma. These tumor harbor t (14;18) translocation in at least 90% of patients. Recently, activating EZH2 mutations have been found in a significant number of patients with FL. Gene expression profiling (GEP) was performed to determine differential gene-expression between the EZH2 mutated vs unmutated subgroups in FL. Total RNA extracted from fresh frozen specimens with FL diagnosis were processed for hybridization to Affymetrix HG-U133 plus 2 arrays. To enhance the identification of differential gene expression in FL tumor cells only, FL cases with a high B-cell content (enriched B-cell signature of >2-fold above the mean of the B-cell signature (pan B-cell markers) in the entire FL data set) were chosen for analysis.

2014-07-01 | E-GEOD-55267 | biostudies-arrayexpress

Human lymphoid stromal cell heterogeneity and functional alteration in follicular lymphoma

Project description:Despite recent advances in the characterization of stromal cell origin, heterogeneity, and function in mice, little is known in human. Follicular lymphoma (FL) is the most frequent indolent lymphoma. It corresponds to the accumulation of germinal center B-cell clones within lymph nodes. FL B cells interact with a reprogrammed immune and stromal cells that provide crucial contributions to the licensing of tumor growth and immune evasion. Most of transcriptomics approaches in human was performed on cultured, and amplified stromal cells modifying their phenotype and function. We purified native stromal cells from LN FL patients, healthy tonsil, and healthy bone marrow. Gene expression profiling based on three lymphoid stromal cell types provides new insights on the characterization of those cells in human and highlight new signalling pathways involved in the crosstalk between stromal cells and tumoral FL B cells.

2021-04-30 | GSE148656 | GEO

Single cell profiling of CD4+ T cells from follicular lymphoma, diffuse large B cell lymphoma and tonsilar samples

Project description:Tumor-infiltrating regulatory T cells contribute to an immunosuppressive tumor microenvironment. We applied single-cell RNA sequencing (scRNA-seq) , TCR sequencing combined with cellular indexing of transcriptomes and epitopes (CITE-seq) on CD4 T cells to decipher the heterogeneity of intratumoral Tregs in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), compared with non-malignant tonsillar tissue.

2023-09-12 | GSE242756 | GEO

Abnormal expression of glucose transporter-1 are a driver of early relapse in follicular lymphoma

Project description:FL patients with high GLUT1 levels are at increased risk for early relapse and show only limited responses to PI3K inhibitors. The development of new therapies requires an understanding of the changes in their tumor immune microenvironment (TIME). Using novel IMC and proteomics techniques, we comprehensively identified distinguishing features in the TIME as a function of GLUT1 levels. Bioinformatics analyses identified a crosstalk between GLUT1 and TIME in tumor development and suggest that FL patients expressing high GLUT1 may benefit from metabolic-modulating therapies to prevent early relapse.

2023-03-11 | PXD031257 | Pride

Affymetrix SNP array data for follicular lymphoma (FL) and transformed follicular lymphoma (tFL) samples

Project description:Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma involving germinal centre B cells, with a subset of patients undergoing transformation to a diffuse large B-cell lymphoma (DLBCL) morphology for which the clinical outcomes are poor. To elucidate the differences in copy number profiles between FL and tFL groups, we performed Affymetrix SNP 6.0 Array analysis on 31 paired FL-tFL cases. We wanted to identify and compare recurrent somatic copy number alterations (CNAs) between the two groups (FL vs. tFL). In addition, the concordance and discordance in the copy neutral loss of heterozygosity (cnLOH) between the two groups were also investigated to identify recurrent target gene regions.

2013-10-01 | GSE42525 | GEO

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