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

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

PROVIDER: PRJNA841593 | ENA |

REPOSITORIES: ENA

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

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.

2022-05-28 | GSE203610 | GEO

Follicular Lymphoma Microenvironment Characteristics Associated with Tumor Cell Mutations and MHC Class II Expression.

Project description:Follicular lymphoma (FL) is a B-cell malignancy with a complex tumor microenvironment that is rich in nonmalignant immune cells. We applied single-cell RNA sequencing to characterize the diverse tumor and immune cell populations of FL and identified major phenotypic subsets of FL T cells, including a cytotoxic CD4 T-cell population. We characterized four major FL subtypes with differential representation or relative depletion of distinct T-cell subsets. By integrating exome sequencing, we observed that somatic mutations are associated with, but not definitive for, reduced MHC expression on FL cells. In turn, expression of MHCII genes by FL cells was associated with significant differences in the proportions and targetable immunophenotypic characteristics of T cells. This provides a classification framework of the FL microenvironment in association with FL genotypes and MHC expression, and informs different potential immunotherapeutic strategies based upon tumor cell MHCII expression.SignificanceWe have characterized the FL-infiltrating T cells, identified cytotoxic CD4 T cells as an important component that is associated with tumor cell-intrinsic characteristics, and identified sets of targetable immune checkpoints on T cells that differed from FLs with normal versus low MHC expression. See related commentary by Melnick, p. 374. This article is highlighted in the In This Issue feature, p. 369.

| S-EPMC9894575 | biostudies-literature

Equine MHC class II

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mhc class I_SIV

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MHC-Mafa class II 18759

Project description:PacBio sequencing of Macaca fascicularis MHC class II genes.

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Acrocephalus schoenobaenus MHC class I

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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

MHC class II alleles in Great Apes

Project description:MHC class II alleles in Great Apes

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Effect of MHC II expression in pro-B cells: Pre-B cells and follicular B cells from wild-type and MHC II conditional mice

Project description:Hardy’s Fraction D bone marrow pre-B cells and splenic follicular B cells were purified by flow cytometry according to MHC II expression from wild-type and ItgaxcreH2-Ab1c MHC II conditional mice and transcriptionally profiled by RNA-seq. Duplicate or triplicate samples for each genotype and level of MHC II expression were sequenced. This is part of ongoing investigation of a possible cell-intrinsic role of MHC II B cells.

2018-08-07 | E-MTAB-6765 | biostudies-arrayexpress

MHC class I and MHC class II reporter mice enable analysis of immune oligodendroglia in mouse models of multiple sclerosis

Project description:Oligodendrocytes and their progenitors upregulate MHC pathways in response to inflammation, but the frequency of this phenotypic change is unknown and the features of these immune oligodendroglia are poorly defined. We generated MHC class I and II transgenic reporter mice to define their dynamics in response to inflammatory demyelination, providing a means to monitor MHC activation in diverse cell types in living mice and define their roles in aging, injury and disease.

2022-09-23 | GSE213739 | GEO

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