Humanized mouse model of a human B cell lymphoma to study tumor-immune cell interactions
Nicole C. Walsh1, Rachel M. Gerstein2, Benjamin Chen3, Zheng Zhou4, Hong Zhang5, Leonard D. Shultz6, Karl Simin7, Rita Bortell1, Michael A. Brehm1, Jan Cerny4, Jack Leonard2, Bruce Woda3, Andrew Evens8, Dale L. Greiner1 and Alan G. Rosmarin4
1Program in Molecular Medicine, 2Department of Microbiology and Physiological Systems, 3Department of Pathology, 4Department of Medicine, Division of Hematology/Oncology; 5Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01605; 6Jackson Laboratory, Bar Harbor, ME 04609; 7Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Memorial Medical Center, Worcester, MA; 8Division of Hematology/Oncology, Tufts University School of Medicine, Boston, MA
The ability of tumors to evade immune responses contributes to tumor progression, susceptibility to treatment and overall aggressiveness of malignancies. Our understanding of tumor-immune interactions in human cancer is shaped by studies in syngeneic mouse tumor models. Humanized mice generated from patient derived xenografts (PDX) are a promising alternative to traditional mouse models to specifically interrogate the interactions between human tumors and immune systems. Here we studied a high grade B cell lymphoma PDX in NOD-scid IL2rgnull (NSG) mice. A diffuse large B cell lymphoma (DLBCL) grew in 80% of mice that received patient cells, with lymphoma cells in blood and infiltrating the spleen, bone marrow, liver, ovaries, and brain. The lymphoma serially transplanted with high efficiency and rituximab treatment significantly delayed tumor growth. Moreover, the lymphoma grew efficiently in NSG mice engrafted with human immune systems, suggesting that immune-mediated rejection was suppressed. This disseminating B cell lymphoma model will enable studies focused on immune suppressive mechanisms of the tumor and evaluation of novel therapeutics for immune checkpoint blockade.
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