Project description:Follicular lymphoma (FL) shows heterogenous expression of the cell surface B-cell marker, CD20. In order to investigate whether this heterogeneity also marks underlying transcriptional heterogeneity, we sorted tumor B-cells from 8 FL specimens based upon their intermediate or high expression of CD20 and transcriptionally profiled them. CD20 intermediate and CD20 high tumor B-cells were sorted by FACS, RNA extracted, and profiled using Affymetrix U133 plus 2.0 microarrays.
Project description:The clinical utility of T-cell agonistic antibodies in cancer therapy, much less their ability to stimulate intratumoral T-cells in patients, has eluded us. T-cell agonistic antibodies such as anti-CD27 can induce clinically meaningful anti-tumor activity. The combination of anti-CD27 agonist varlilumab and tumor-depleting anti-CD20 rituximab was investigated in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) (RiVa trial;NCT03307746). Our experiments detail RNA-seq data from 21 B-cell NHL patients, including both pre and on-treatment biopsies taken from lymph nodes.
Project description:Follicular lymphoma (FL) shows heterogenous expression of the cell surface B-cell marker, CD20. In order to investigate whether this heterogeneity also marks underlying transcriptional heterogeneity, we sorted tumor B-cells from 8 FL specimens based upon their intermediate or high expression of CD20 and transcriptionally profiled them.
Project description:The clinical utility of T-cell agonistic antibodies in cancer therapy, much less their ability to stimulate intratumoral T-cells in patients, has eluded us. T-cell agonistic antibodies such as anti-CD27 can induce clinically meaningful anti-tumor activity. The combination of anti-CD27 agonist varlilumab and tumor-depleting anti-CD20 rituximab was investigated in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) (RiVa trial;NCT03307746). Our experiments detail scRNA-seq data from 6 B-cell NHL patients, including both pre and on-treatment biopsies taken from lymph nodes.
Project description:The goal of this study was to investigate the effect of intratumoral injection of GLA-SE, a TLR4 agonist in stable emulsion (SE), in Balb/c mice with established A20 lymphoma.
Project description:Biological heterogeneity in diffuse large B cell lymphoma (DLBCL) is partly driven by cell-of-origin subtypes and associated genomic lesions, but also by diverse cell types and cell states in the tumor microenvironment (TME). However, dissecting these cell states and their clinical relevance at scale remains challenging. Here, we implemented EcoTyper, a machine learning framework integrating transcriptome deconvolution and single-cell RNA sequencing, to characterize clinically relevant DLBCL cell states and ecosystems. Using this approach, we identified five cell states of malignant B cells that vary in prognostic associations and differentiation status. We also identified striking variation in cell states for 12 other lineages comprising the TME and forming cell-state interactions in stereotyped ecosystems. While cell-of-origin subtypes have distinct TME composition, DLBCL ecosystems capture clinical heterogeneity within existing subtypes and extend beyond cell-of-origin and genotypic classes. These results resolve the DLBCL microenvironment at unprecedented resolution and identify opportunities for therapeutic targeting (https://ecotyper-stanford-edu.stanford.idm.oclc.org/lymphoma).
Project description:Biological heterogeneity in diffuse large B cell lymphoma (DLBCL) is partly driven by cell-of-origin subtypes and associated genomic lesions, but also by diverse cell types and cell states in the tumor microenvironment (TME). However, dissecting these cell states and their clinical relevance at scale remains challenging. Here, we implemented EcoTyper, a machine learning framework integrating transcriptome deconvolution and single-cell RNA sequencing, to characterize clinically relevant DLBCL cell states and ecosystems. Using this approach, we identified five cell states of malignant B cells that vary in prognostic associations and differentiation status. We also identified striking variation in cell states for 12 other lineages comprising the TME and forming cell-state interactions in stereotyped ecosystems. While cell-of-origin subtypes have distinct TME composition, DLBCL ecosystems capture clinical heterogeneity within existing subtypes and extend beyond cell-of-origin and genotypic classes. These results resolve the DLBCL microenvironment at unprecedented resolution and identify opportunities for therapeutic targeting (https://ecotyper-stanford-edu.stanford.idm.oclc.org/lymphoma).