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Large B-cell lymphoma microenvironment archetype profiles (LymphoMAPs). [macrophage]

ABSTRACT: Large B-cell lymphoma microenvironment archetype profiles (LymphoMAPs). [macrophage]

PROVIDER: PRJNA1267063 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR33689421_1.fastq.gz	Fastqsanger.gz
	SRR33689421_2.fastq.gz	Fastqsanger.gz
	SRR33689422_1.fastq.gz	Fastqsanger.gz
	SRR33689422_2.fastq.gz	Fastqsanger.gz
	SRR33689423_1.fastq.gz	Fastqsanger.gz

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Large B-cell lymphoma microenvironment archetype profiles (LymphoMAPs). [macrophage]

Project description:Large B-cell lymphomas (LBCL) are clinically and biologically heterogeneous lymphoid malignancies with complex microenvironments that are central to disease etiology. Here we have employed single-nucleus multiome profiling of 232 tumor and control biopsies to characterize diverse cell types and subsets that are present in LBCL tumors, effectively capturing the lymphoid, myeloid, and non-hematopoietic cell compartments. Cell subsets co-occurred in stereotypical Lymphoma Microenvironment Archetype Profiles (LymphoMAPs) defined by; (i) a sparsity of T-cells and high frequencies of cancer-associated fibroblasts and tumor-associated macrophages [FMAC]; (ii) lymph node architectural cell types with naïve and memory T-cells [LN]; or (iii) activated macrophages and exhausted CD8 T-cells [TEX]. Divergent patterns of cell-cell communication underpinned the transcriptional phenotypes of archetype-defining cell subsets resulting in exclusion, support or suppression of T-cells, respectively. Consistent with this, LymphoMAPs were associated with significantly different clinical outcomes following CD19 CAR T-cell therapy.

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Project description:Diffuse large B-cell lymphoma (DLBCL) is a disease with heterogeneous outcome. Stromal signatures have been correlated to survival in DLBCL. Their use, however, is hampered by the lack of assays for formalin-fixed paraffin-embedded material (FFPE). We constructed a lymphoma-associated macrophage interaction signature (LAMIS) interrogating features of the microenvironment using a NanoString assay applicable to FFPE. The clinical impact of the signature could be validated in a cohort of 466 patients enrolled in prospective clinical trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Patients with high expression of the signature (LAMIShigh) had shorter EFS, PFS, and OS. Multivariate analyses revealed independence from IPI factors in EFS (HR 1.7, 95% CI 1.2–2.4, p-value = 0.001), PFS (HR 1.8, 95% CI 1.2–2.5, p-value = 0.001) and OS (HR 1.8, 95% CI 1.3–2.7, p-value = 0.001). Multivariate analyses adjusted for the IPI factors showed the signature to be independent from COO, MYC rearrangements and double expresser status (DE). LAMIShigh and simultaneous DE status characterized a patient subgroup with dismal prognosis and early relapse. Our data underline the importance of the microenvironment in prognosis. Combined analysis of stromal features, the IPI and DE may provide a new rationale for targeted therapy.

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