Flow Cytometry of Diffuse Large B-Cell Lymphoma (Symphony cohort, 2 of 3)
Description
This dataset is the 2nd of 3 parts and contains 23-color flow cytometry data from 133 diffuse large B-cell lymphoma (DLB) and 15 reactive lymph node (RLN) diagnostic biopsy samples. Each sample was stained with a 22-antibody T cell panel and data were acquired on a BD FACS Symphony instrument. The samples were acquired across 5 separate batch runs (#1-5). Each batch run also included an aliquot from a pool of 13 different RLN samples to serve as an internal staining/acquisition batch control. The file naming format is "SymT2_DLB_A1234" where "Sym" = Symphony, "T" = T cell panel, "2" = batch #2 (or 1, 3, 4, or 5), "DLB" = diffuse large B-cell lymphoma (or "RLN" = reactive lymph node), and "A1234" = unique sample identifier (or "pooled" = a pool of like samples). Diffuse large B-cell lymphoma is a common malignancy of mature B cells with heterogeneous outcomes. Prior studies have defined poor prognosis subtypes by features such as cell-of-origin; however, the role of the immune microenvironment in defining clinical outcomes is less clear. Here we used highly dimensional mass and flow cytometry with up to 40 and 22 antibody markers, respectively, to derive a single cell-resolved map of the tumor ecosystem encompassing both B- and T-cell compartments, along with reactive lymph node controls. Unlike our recent findings in follicular lymphoma (FL), B-cell phenotypes were largely unique to each patient and intratumoral diversity was neither prominent nor correlated with clinical outcome. Among tumor infiltrating T-cells, multidimensional analysis yielded 23-25 distinct clusters representing the full spectrum of activation/maturation states including terminally differentiated subsets which identified patients with inferior clinical outcome amongst a discovery cohort of 123 patients. Importantly, this observation was validated in an independent cohort of 151 patients using a single marker of terminal differentiation, CD57, in combination with routine CD4/CD8 T cell subsetting markers thus simplifying translation to routine clinical practice. The significance of CD8+ CD57+ T-cells was independent of cell-of-origin classification, suggesting this immune response feature is relevant across DLBCL subtypes. T-cell profiling can thus provide insight into potential tumor/immune cell interactions and may inform selection of immune-directed therapies.
Files
Institutions
- BC Cancer Agency Vancouver Centre
- The University of British Columbia
Categories
Funders
- Leukemia and Lymphoma SocietyUnited States
- BC Cancer FoundationCanada