title: Stem Cell Transfusion Restores Immune Function in Radiation-Induced Lymphopenic C57BL/6 Mice.
abstract: Radiation-induced lymphopenia (RIL) is associated with treatment of different tumors (lung, colon, pancreas, breast, sarcomas, and glioblastoma). It is a significant clinical problem affecting the survival of cancer patients. The biologic mechanisms leading to RIL are not clearly understood. In this study, we established a mouse model of RIL representing therapeutic clinical regimen for lung cancer. Flow cytometry was used to analyze circulating levels of T and B cells and bone marrow (BM) stem cells. We found that fractionated radiation to the thorax significantly reduced circulating T and B cells as well as BM stem cells. Ex-vivo irradiation of blood and autologous reinjection to mice also significantly induced lymphopenia. Furthermore, we found that mobilization of stem cells from the BM and autologous stem cell transplant rescued RIL in mice. Overall, our results suggest that RIL has not only direct effect on circulating lymphocytes, but also has indirect effect on circulating lymphocytes as well as stem cells in the nonirradiated BM. These results open a new window for investigating the direct and indirect biologic mechanisms leading to RIL, and provide a preclinical basis to test the effect of stem cell transplantation for treatment of RIL in cancer patients.
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Kapoor
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Arpine
authors.initials: A
authors.lastname: Khudanyan
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Pilar
authors.initials: P
authors.lastname: de la Puente
authors.affiliation: Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, Missouri. Department of Medicine, Oncology Division, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Jian
authors.initials: J
authors.lastname: Campian
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis School of Medicine, St. Louis, Missouri. Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, Missouri. Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Hallahan
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis School of Medicine, St. Louis, Missouri. Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, Missouri. dthotala@radonc.wustl.edu aazab@radonc.wustl.edu.
authors.forename: Abdel Kareem
authors.initials: AK
authors.lastname: Azab
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis School of Medicine, St. Louis, Missouri. Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, Missouri. dthotala@radonc.wustl.edu aazab@radonc.wustl.edu.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Thotala
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D008231:Lymphopenia / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D011878:Radiotherapy / Q000009:adverse effects*; D013234:Stem Cells / Q000473:pathology / Q000528:radiation effects