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Direct in vivo evidence for B-cell receptor and NF-KB activation in mantle cell lymphoma: role of the lymph node microenvironment and activating mutations.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE70927 | GEO | 2016/07/15

SECONDARY ACCESSION(S): PRJNA289960

REPOSITORIES: GEO

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Direct in vivo evidence for B-cell receptor and NF-KB activation in mantle cell lymphoma: role of the lymph node microenvironment and activating mutations.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-07-15 | E-GEOD-70927 | biostudies-arrayexpress

Direct in vivo evidence for B-cell receptor and NF-KB activation in mantle cell lymphoma: role of the lymph node microenvironment and activating mutations. [Affymetrix]

Project description:We provide direct in vivo evidence for activation of the BCR and canonical NF-KB pathways in MCL that, in the absence of activating mutations, is dependent on the lymph node microenvironment. This finding provides a mechanistic explanation for the surprising efficacy of ibrutinib for the treatment of this type of lymphoma. Mutations in components of the BCR and NF-KB pathways are associated with cell-autonomous signaling and resistance to ibrutinib. Lymph node biopsies and peripheral blood samples were obtained from 55 patients with previously untreated MCL. The samples are distributed into 3 groups: peripheral blood (purified CD19, N=17), unpurified lymph node biopsy (mixed tissue biopsy, N=34), and purified lymph node (purified CD19 Tumor, N=4).

2016-07-15 | E-GEOD-70910 | biostudies-arrayexpress

Direct in vivo evidence for B-cell receptor and NF-KB activation in mantle cell lymphoma: role of the lymph node microenvironment and activating mutations. [RNA-Seq]

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Direct in vivo evidence for B-cell receptor and NF-KB activation in mantle cell lymphoma: role of the lymph node microenvironment and activating mutations. [Affymetrix]

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Direct in vivo evidence for B-cell receptor and NF-KB activation in mantle cell lymphoma: role of the lymph node microenvironment and activating mutations. [RNA-Seq]

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Direct in vivo evidence for B-cell receptor and NF-KB activation in mantle cell lymphoma: role of the lymph node microenvironment and activating mutations.

Project description:Direct in vivo evidence for B-cell receptor and NF-KB activation in mantle cell lymphoma: role of the lymph node microenvironment and activating mutations.

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Harnessing the lymph node microenvironment.

Project description:Purpose of reviewTo evaluate role of the lymph node in immune regulation and tolerance in transplantation and recent advances in the delivery of antigen and immune modulatory signals to the lymph node.Recent findingsLymph nodes are a primary site of immune cell priming, activation, and modulation, and changes within the lymph node microenvironment have the potential to induce specific regulation, suppression, and potentially tolerance. Antigen enters the lymph node either from tissues via lymphatics, from blood via high endothelial venules, or directly via injection. Here we review different techniques and materials to deliver antigen to the lymph node including microparticles or nanoparticles, ex-vivo antigen presenting cell manipulation, and use of receptor conjugation for specific intralymph node targeting locations.SummaryThe promising results point to powerful techniques to harness the lymph node microenvironment and direct systemic immune regulation. The materials, techniques, and approaches suggest that translational and clinical trials in nonhuman primate and patients may soon be possible.

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Follicular lymphoma lymph node

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A novel patient-derived 3D model recapitulates mantle cell lymphoma lymph node signaling, immune profile and in vivo ibrutinib responses.

Project description:Mantle cell lymphoma (MCL), a rare and aggressive B-cell non-Hodgkin lymphoma, mainly develops in the lymph node (LN) and creates a protective and immunosuppressive niche that facilitates tumor survival, proliferation and chemoresistance. To capture disease heterogeneity and tumor microenvironment (TME) cues, we have developed the first patient-derived MCL spheroids (MCL-PDLS) that recapitulate tumor oncogenic pathways and immune microenvironment in a multiplexed system that allows easy drug screening, including immunotherapies. MCL spheroids, integrated by tumor B cells, monocytes and autologous T-cells self-organize in disc-shaped structures, where B and T-cells maintain viability and proliferate, and monocytes differentiate into M2-like macrophages. RNA-seq analysis demonstrated that tumor cells recapitulate hallmarks of MCL-LN (proliferation, NF-kB and BCR), with T cells exhibiting an exhaustion profile (PD1, TIM-3 and TIGIT). MCL-PDLS reproduces in vivo responses to ibrutinib and demonstrates that combination of ibrutinib with nivolumab (anti-PD1) may be effective in ibrutinib-resistant cases by engaging an immune response with increased interferon gamma and granzyme B release. In conclusion, MCL-PDLS recapitulates specific MCL-LN features and in vivo responses to ibrutinib, representing a robust tool to study MCL interaction with the immune TME and to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.

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