The use of cancer immunotherapies can result in severe toxic effects. As cancer is primarily a disease of ageing, Mirsoian et al. have examined the toxicity of immunotherapy in aged mice. The authors previously showed that treatment of young mice with an immune-stimulatory therapy including interleukin-2 (IL-2) and a monoclonal antibody against CD40 (anti-CD40) reduced tumour growth and was well tolerated. However, in aged mice this treatment induced a cytokine storm that was 100% lethal. They have now found that levels of visceral fat in mice increase with age. Young obese mice have similar levels of visceral fat to aged mice, and IL-2 and anti-CD40 treatment also induces a lethal cytokine storm in these mice, whereas calorie-restricted aged mice have less visceral fat and are protected from treatment toxicity.
References
Mirsoian, A. et al. Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged mice. J. Exp. Med. http://dx.doi.org/10.1084/jem.20140116 (2014)
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Seton-Rogers, S. A lethal storm. Nat Rev Cancer 14, 766 (2014). https://doi.org/10.1038/nrc3868
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DOI: https://doi.org/10.1038/nrc3868