ATM-dependent spontaneous regression of early Eμ-myc-induced murine B-cell leukemia depends on natural killer and T cells.
Mechanisms of spontaneous tumor regression have been difficult to characterize in a systematic manner due to their rare occurrence and the lack of model systems. Here, we provide evidence that early-stage B cells in Eμ-myc mice are tumorigenic and sharply regress in the periphery between 41 and 65 days of age. Regression depended on CD4(+), CD8(+), NK1.1(+) cells and the activation of the DNA damage response, which has been shown to provide an early barrier against cancer. The DNA damage response can induce ligands that enhance immune recognition. Blockade of DNAM-1, a receptor for one such ligand, impaired tumor regression. Hence, Eμ-myc mice provide a model to study spontaneous regression and possible mechanisms of immune evasion or suppression by cancer cells.
Immunology Programme, Centre of Life Sciences, Department of Microbiology, National University of Singapore, Singapore.
J Ludovic
JL
Croxford
Melissa Li Fang
ML
Tang
Meng Fei
MF
Pan
Caleb Weihao
CW
Huang
Neha
N
Kamran
Cindy Meow Ling
CM
Phua
Wee Joo
WJ
Chng
Siok Bian
SB
Ng
David H
DH
Raulet
Stephan
S
Gasser
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D016259:Genes, myc / Q000502:physiology; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015448:Leukemia, B-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009365:Neoplasm Regression, Spontaneous / Q000235:genetics* / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007148:Immunoglobulin mu-Chains; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases