A Human Lymphoma Organoid Model for Evaluating and Targeting the Follicular Lymphoma Tumor Immune Microenvironment

Heterogeneity in the tumor microenvironment (TME) of follicular lymphoma (FL) can affect clinical outcomes. We developed a new organoid culture method for cultivating patient-derived lymphoma organoids (PDLOs), which include cells from the native FL TME. We generated organoids from 12 FL patients at diagnosis, clinical progression, or relapse. These organoids were profiled with targeted DNA sequencing and mRNA sequencing. We evaluated the stability of organoids in culture at serial weekly timepoints (D0, D7, D14, D21). We treated organoids with CD19:CD3 or CD20:CD3 bispecific antibodies or unconjugated anti-CD20, anti-CD19, and anti-CD3 as a control, and profiled DNA/RNA at D11 to evaluate treatment response. This system is intended as a platform for advancing precision medicine efforts in FL through patient-specific modeling, high-throughput screening, TME signature identification, and treatment response evaluation.]]>
Inclusion criteria: Viable tumor cell suspensions from patients with follicular lymphoma (FL) at diagnosis, progression, or relapse.Exclusion criteria: Lymphoma histologies other than FL or transformed FL.]]>
The study was conducted with primary FL samples collected at Stanford University. All patients underwent informed consent on an IRB-approved protocol. Organoid experiments, flow cytometry, and RNA sequencing were performed at UC Irvine, while DNA sequencing and bioinformatic analysis were performed at Stanford University.]]>