Transplantation of Unirradiated Bone Marrow Cells after Total-Body Irradiation Prevents the Development of Thymic Lymphoma in Mice through Niche Competition.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Hasapis, S; Caraballo, I; Lee, C-L

Published Date

  • March 1, 2021

Published In

Volume / Issue

  • 195 / 3

Start / End Page

  • 301 - 306

PubMed ID

  • 33347573

Pubmed Central ID

  • PMC8240018

Electronic International Standard Serial Number (EISSN)

  • 1938-5404

Digital Object Identifier (DOI)

  • 10.1667/RADE-20-00221.1

Language

  • eng

Conference Location

  • United States