Changes in the activation and reconstitution of lymphocytes resulting from total-body irradiation correlate with slowed tumor growth.
Alterations in cytokine secretion, activation marker expression, and immune cell concentrations were investigated at sequential time points following delivery of total-body irradiation (TBI) to C57BL/6 mice (n = 64) in the Lewis lung tumor model. Significantly slower tumor growth was observed when a 3-Gy dose of TBI was administered 2 h prior to tumor implantation (p < 0.05). The antitumor effect was correlated with an increased CD4:CD8 T cell ratio and heightened leukocyte blastogenesis. TBI was also found to induce an expansion of natural killer (NK) cells in the blood and spleen of tumor-bearing animals 10 days after irradiation (2.8 x 10(6) NK cells/spleen in test mice compared to 8.9 x 10(5) NK cells/spleen in normal control animals). However, no significant differences were found in NK cell levels within the tumor tissue. Enhanced production of interleukin (IL)-12 and IL-18 from spleen supernatants was consistent with an augmentation of the NK cell response. Significant reductions in transforming growth factor-beta1 (TGF-beta1) and vascular endothelial growth factor, both of which are associated with immune suppression, were also noted. Furthermore, TBI induced changes in expression of CD25 and CD71 activation markers, suggesting that radiation may alter tumor surveillance. Taken together, the relative percentages and activation status of immune cell compartments support the conclusion that these TBI-induced changes function to slow tumor progression.
Miller
Glen M
GM
Division of Microbiology and Molecular Genetics, Loma Linda University and Medical Center, Loma Linda, CA 92354, USA. gmiller@som.llu.edu
Kim
Dong W
DW
Andres
Melba L
ML
Green
Lora M
LM
Gridley
Daila S
DS
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000532:radiotherapy*; D003037:Cobalt Radioisotopes; D016207:Cytokines / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000528:radiation effects; D007694:Killer Cells, Natural / Q000276:immunology / Q000528:radiation effects; D007958:Leukocyte Count; D008175:Lung Neoplasms / Q000097:blood / Q000276:immunology / Q000532:radiotherapy*; D008213:Lymphocyte Activation / Q000528:radiation effects*; D008214:Lymphocytes / Q000276:immunology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011879:Radiotherapy Dosage; D013154:Spleen / Q000276:immunology / Q000528:radiation effects; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000637:transplantation; D014916:Whole-Body Irradiation
D003037:Cobalt Radioisotopes; D016207:Cytokines