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

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. Overall design: Tonsillar fibroblastic reticular cells (tFRCs) were isolated from fresh tonsils. The cells were passaged for six generations in Insulin-Transferrin-Selenium (Thermo Fisher) containing Dulbecco's Modified Eagle Medium (DMEM, Corning) supplemented with 10% fetal Bovine serum (FBS) and Penicillin (100 units/mL)-streptomycin (100 µg/mL). The tFRCs were stimulated with 10 ng/mL and 50 ng/mL TGFB (Peprotech). The cells were harvested after 48 hours post treatment and subjected to bulk RNA sequencing.