Open AccessTransplantation of Unirradiated Bone Marrow Cells after Total-Body Irradiation Prevents the Development of Thymic Lymphoma in Mice through Niche Competition
Author(s) -
Stephanie Hasapis,
Isibel Caraballo,
Chang-Lung Lee
Publication year - 2020
Publication title -
radiation research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 124
eISSN - 1938-5404
pISSN - 0033-7587
DOI - 10.1667/rade-20-00221.1
Subject(s) - immunosurveillance , lymphoma , bone marrow , lymphopoiesis , thymoma , biology , transplantation , thymectomy , cancer research , total body irradiation , immunology , tumor necrosis factor alpha , pathology , haematopoiesis , stem cell , immune system , medicine , microbiology and biotechnology , chemotherapy , cyclophosphamide , myasthenia gravis , genetics
Mouse models of radiation-induced thymic lymphoma are commonly used to study the biological effects of total-body irradiation (TBI) on the formation of hematologic malignancies. It is well documented that radiation-induced thymic lymphoma can be inhibited by protecting the bone marrow (BM) from irradiation; however, the mechanisms underlying this phenomenon are poorly understood. Here, we aimed to address this question by performing transplantation of BM cells from genetically engineered mice that have defects in tumor immunosurveillance or occupying different thymic niches. We found that BM cells from mice that have impaired tumor immunosurveillance, by deleting tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ) or perforin-1 (PRF1), remained sufficient to suppress the formation of radiation-induced thymic lymphoma. On the other hand, BM cells from Rag2-/-; γc-/- mice and Rag2-/- mice, which have defects in occupying thymic niches beyond double negative (DN2) and DN3, respectively, failed to inhibit radiation-induced lymphomagenesis in the thymus. Taken together, based on our findings, we propose a model where unirradiated BM cells suppress radiation-induced lymphomagenesis in the thymus by competing with tumor-initiating cells for thymic niches beyond the DN3 stage.